LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 5 of total 5

Search options

  1. Article ; Online: FOXC2 promotes vasculogenic mimicry and resistance to anti-angiogenic therapy.

    Cannell, Ian G / Sawicka, Kirsty / Pearsall, Isabella / Wild, Sophia A / Deighton, Lauren / Pearsall, Sarah M / Lerda, Giulia / Joud, Fadwa / Khan, Showkhin / Bruna, Alejandra / Simpson, Kathryn L / Mulvey, Claire M / Nugent, Fiona / Qosaj, Fatime / Bressan, Dario / Dive, Caroline / Caldas, Carlos / Hannon, Gregory J

    Cell reports

    2023  Volume 42, Issue 8, Page(s) 112791

    Abstract: Vasculogenic mimicry (VM) describes the formation of pseudo blood vessels constructed of tumor cells that have acquired endothelial-like properties. VM channels endow the tumor with a tumor-derived vascular system that directly connects to host blood ... ...

    Abstract Vasculogenic mimicry (VM) describes the formation of pseudo blood vessels constructed of tumor cells that have acquired endothelial-like properties. VM channels endow the tumor with a tumor-derived vascular system that directly connects to host blood vessels, and their presence is generally associated with poor patient prognosis. Here we show that the transcription factor, Foxc2, promotes VM in diverse solid tumor types by driving ectopic expression of endothelial genes in tumor cells, a process that is stimulated by hypoxia. VM-proficient tumors are resistant to anti-angiogenic therapy, and suppression of Foxc2 augments response. This work establishes co-option of an embryonic endothelial transcription factor by tumor cells as a key mechanism driving VM proclivity and motivates the search for VM-inhibitory agents that could form the basis of combination therapies with anti-angiogenics.
    MeSH term(s) Humans ; Neovascularization, Pathologic/metabolism ; Cell Line, Tumor ; Immunotherapy
    Language English
    Publishing date 2023-07-26
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2023.112791
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    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.

  2. Article ; Online: A conserved YAP/Notch/REST network controls the neuroendocrine cell fate in the lungs.

    Shue, Yan Ting / Drainas, Alexandros P / Li, Nancy Yanzhe / Pearsall, Sarah M / Morgan, Derrick / Sinnott-Armstrong, Nasa / Hipkins, Susan Q / Coles, Garry L / Lim, Jing Shan / Oro, Anthony E / Simpson, Kathryn L / Dive, Caroline / Sage, Julien

    Nature communications

    2022  Volume 13, Issue 1, Page(s) 2690

    Abstract: The Notch pathway is a conserved cell-cell communication pathway that controls cell fate decisions. Here we sought to determine how Notch pathway activation inhibits the neuroendocrine cell fate in the lungs, an archetypal process for cell fate decisions ...

    Abstract The Notch pathway is a conserved cell-cell communication pathway that controls cell fate decisions. Here we sought to determine how Notch pathway activation inhibits the neuroendocrine cell fate in the lungs, an archetypal process for cell fate decisions orchestrated by Notch signaling that has remained poorly understood at the molecular level. Using intratumoral heterogeneity in small-cell lung cancer as a tractable model system, we uncovered a role for the transcriptional regulators REST and YAP as promoters of the neuroendocrine to non-neuroendocrine transition. We further identified the specific neuroendocrine gene programs repressed by REST downstream of Notch in this process. Importantly, we validated the importance of REST and YAP in neuroendocrine to non-neuroendocrine cell fate switches in both developmental and tissue repair processes in the lungs. Altogether, these experiments identify conserved roles for REST and YAP in Notch-driven inhibition of the neuroendocrine cell fate in embryonic lungs, adult lungs, and lung cancer.
    MeSH term(s) Cell Differentiation/genetics ; Humans ; Lung/metabolism ; Lung Neoplasms/genetics ; Lung Neoplasms/metabolism ; Neuroendocrine Cells/metabolism ; Receptors, Notch/genetics ; Receptors, Notch/metabolism
    Chemical Substances Receptors, Notch
    Language English
    Publishing date 2022-05-16
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-022-30416-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    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.

  3. Book ; Online: Atlantic families

    Pearsall, Sarah M. S

    lives and letters in the later eighteenth century

    (Oxford scholarship online)

    2008  

    Abstract: The Atlantic represented a world of opportunity in the eighteenth century, but it represented division also, separating families across its coasts. Whether due to economic shifts, changing political landscapes, imperial ambitions, or even simply personal ...

    Author's details Sarah M.S. Pearsall
    Series title Oxford scholarship online
    Abstract The Atlantic represented a world of opportunity in the eighteenth century, but it represented division also, separating families across its coasts. Whether due to economic shifts, changing political landscapes, imperial ambitions, or even simply personal tragedy, many families found themselves fractured and disoriented by the growth and later fissure of a larger Atlantic world. Such dislocation posed considerable challenges to all individuals who viewed orderly family relations asboth a general and a personal ideal. The more fortunate individuals who thus found themselves divided by the Atlant
    Keywords American letters/History and criticism ; English letters/History and criticism ; Families/History ; Letter writing/History
    Language English
    Size Online-Ressource
    Publisher Oxford Univ. Press
    Publishing place New York u.a.
    Document type Book ; Online
    Note Includes bibliographical references (p. [248]-281) and index
    ISBN 9780199532995 ; 0199532990
    DOI 10.1093/acprof:oso/9780199532995.001.0001
    Database Library catalogue of the German National Library of Science and Technology (TIB), Hannover

    More links

    Kategorien

    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.

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  4. Article ; Online: The Rare YAP1 Subtype of SCLC Revisited in a Biobank of 39 Circulating Tumor Cell Patient Derived Explant Models: A Brief Report.

    Pearsall, Sarah M / Humphrey, Sam / Revill, Mitchell / Morgan, Derrick / Frese, Kristopher K / Galvin, Melanie / Kerr, Alastair / Carter, Mathew / Priest, Lynsey / Blackhall, Fiona / Simpson, Kathryn L / Dive, Caroline

    Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer

    2020  Volume 15, Issue 12, Page(s) 1836–1843

    Abstract: Introduction: Recent consensus defines four SCLC subtypes on the basis of transcription factor expression: ASCL1, NEUROD1, POU2F3, and YAP1. The rare YAP1 subtype is associated with "neuroendocrine (NE)-low" cells among SCLC cell lines and patient ... ...

    Abstract Introduction: Recent consensus defines four SCLC subtypes on the basis of transcription factor expression: ASCL1, NEUROD1, POU2F3, and YAP1. The rare YAP1 subtype is associated with "neuroendocrine (NE)-low" cells among SCLC cell lines and patient samples. We evaluated YAP1 in 39 patients with phenotypically diverse circulating tumor cell-derived explant (CDX) models and revisited YAP1 in terms of prevalence, cell phenotype, and intertumor and intratumor heterogeneity.
    Methods: YAP1 transcript and protein expression were assessed by RNA sequencing and immunohistochemistry or multiplexed immunofluorescence of NE and non-NE CDX subpopulations. Physically separated NE and non-NE CDX ex vivo culture lysates were Western blotted for YAP1, NE marker SYP, and AXL.
    Results: RNA sequencing normalized for the four subtype transcription factors identified YAP1 expression in 14 of 39 CDX. A total of 10 CDX expressed YAP1 protein, and eight had strong YAP1 expression confined to rare non-NE cell clusters. This was confirmed in ex vivo CDX cultures in which adherent non-NE cells lacking SYP expression expressed YAP1. However, in two CDX, weaker cellular YAP1 expression was observed, widely dispersed in SYP-positive NE cells.
    Conclusions: YAP1 was predominantly expressed in non-NE cell clusters in SCLC CDX, but two of 39 CDX expressed YAP1 in NE cells. CDX22P, with relatively high YAP1 expression, is an ASCL1 NE subtype with a low NE score and an outlier within this subtype in our CDX biobank. These descriptive data reveal subtly different YAP1 expression profiles, paving the way for functional studies to compare YAP1 signaling in non-NE and low NE cell contexts for potentially personalized therapeutic approaches.
    MeSH term(s) Adaptor Proteins, Signal Transducing/genetics ; Biological Specimen Banks ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms/genetics ; Neoplastic Cells, Circulating ; Transcription Factors/genetics ; YAP-Signaling Proteins
    Chemical Substances Adaptor Proteins, Signal Transducing ; Transcription Factors ; YAP-Signaling Proteins ; YAP1 protein, human
    Language English
    Publishing date 2020-07-25
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2432037-7
    ISSN 1556-1380 ; 1556-0864
    ISSN (online) 1556-1380
    ISSN 1556-0864
    DOI 10.1016/j.jtho.2020.07.008
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 6664: 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.MO 652: Show issues

    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.

  5. Article ; Online: Lineage Plasticity in SCLC Generates Non-Neuroendocrine Cells Primed for Vasculogenic Mimicry.

    Pearsall, Sarah M / Williamson, Stuart C / Humphrey, Sam / Hughes, Ellyn / Morgan, Derrick / García Marqués, Fernando J / Awanis, Griselda / Carroll, Rebecca / Burks, Laura / Shue, Yan Ting / Bermudez, Abel / Frese, Kristopher K / Galvin, Melanie / Carter, Mathew / Priest, Lynsey / Kerr, Alastair / Zhou, Cong / Oliver, Trudy G / Humphries, Jonathan D /
    Humphries, Martin J / Blackhall, Fiona / Cannell, Ian G / Pitteri, Sharon J / Hannon, Gregory J / Sage, Julien / Dive, Caroline / Simpson, Kathryn L

    Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer

    2023  Volume 18, Issue 10, Page(s) 1362–1385

    Abstract: Introduction: Vasculogenic mimicry (VM), the process of tumor cell transdifferentiation to endow endothelial-like characteristics supporting de novo vessel formation, is associated with poor prognosis in several tumor types, including SCLC. In ... ...

    Abstract Introduction: Vasculogenic mimicry (VM), the process of tumor cell transdifferentiation to endow endothelial-like characteristics supporting de novo vessel formation, is associated with poor prognosis in several tumor types, including SCLC. In genetically engineered mouse models (GEMMs) of SCLC, NOTCH, and MYC co-operate to drive a neuroendocrine (NE) to non-NE phenotypic switch, and co-operation between NE and non-NE cells is required for metastasis. Here, we define the phenotype of VM-competent cells and molecular mechanisms underpinning SCLC VM using circulating tumor cell-derived explant (CDX) models and GEMMs.
    Methods: We analyzed perfusion within VM vessels and their association with NE and non-NE phenotypes using multiplex immunohistochemistry in CDX, GEMMs, and patient biopsies. We evaluated their three-dimensional structure and defined collagen-integrin interactions.
    Results: We found that VM vessels are present in 23/25 CDX models, 2 GEMMs, and in 20 patient biopsies of SCLC. Perfused VM vessels support tumor growth and only NOTCH-active non-NE cells are VM-competent in vivo and ex vivo, expressing pseudohypoxia, blood vessel development, and extracellular matrix organization signatures. On Matrigel, VM-primed non-NE cells remodel extracellular matrix into hollow tubules in an integrin β1-dependent process.
    Conclusions: We identified VM as an exemplar of functional heterogeneity and plasticity in SCLC and these findings take considerable steps toward understanding the molecular events that enable VM. These results support therapeutic co-targeting of both NE and non-NE cells to curtail SCLC progression and to improve the outcomes of patients with SCLC in the future.
    MeSH term(s) Animals ; Mice ; Humans ; Lung Neoplasms/pathology ; Neovascularization, Pathologic/genetics ; Cell Transdifferentiation ; Cell Line, Tumor
    Language English
    Publishing date 2023-07-16
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2432037-7
    ISSN 1556-1380 ; 1556-0864
    ISSN (online) 1556-1380
    ISSN 1556-0864
    DOI 10.1016/j.jtho.2023.07.012
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 6664: 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.MO 652: Show issues

    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.

To top