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  1. Article ; Online: Cancer-associated fibroblasts expressing fibroblast activation protein and podoplanin in non-small cell lung cancer predict poor clinical outcome.

    Mathieson, Layla / Koppensteiner, Lilian / Dorward, David A / O'Connor, Richard A / Akram, Ahsan R

    British journal of cancer

    2024  

    Abstract: Background: Cancer-associated fibroblasts (CAFs) are a dominant cell type in the stroma of non-small cell lung cancer (NSCLC). Fibroblast heterogeneity reflects subpopulations of CAFs, which can influence prognosis and treatment efficacy. We describe ... ...

    Abstract Background: Cancer-associated fibroblasts (CAFs) are a dominant cell type in the stroma of non-small cell lung cancer (NSCLC). Fibroblast heterogeneity reflects subpopulations of CAFs, which can influence prognosis and treatment efficacy. We describe the subtypes of CAFs in NSCLC.
    Methods: Primary human NSCLC resections were assessed by flow cytometry and multiplex immunofluorescence for markers of fibroblast activation which allowed identification of CAF subsets. Survival data were analysed for our NSCLC cohort consisting of 163 patients to understand prognostic significance of CAF subsets.
    Results: We identified five CAF populations, termed CAF S1-S5. CAF-S5 represents a previously undescribed population, and express FAP and PDPN but lack the myofibroblast marker αSMA, whereas CAF-S1 populations express all three. CAF-S5 are spatially further from tumour regions then CAF-S1 and scRNA data demonstrate an inflammatory phenotype. The presence of CAF-S1 or CAF-S5 is correlated to worse survival outcome in NSCLC, despite curative resection, highlighting the prognostic importance of CAF subtypes in NSCLC. TCGA data suggest the predominance of CAF-S5 has a poor prognosis across several cancer types.
    Conclusion: This study describes the fibroblast heterogeneity in NSCLC and the prognostic importance of the novel CAF-S5 subset where its presence correlates to worse survival outcome.
    Language English
    Publishing date 2024-04-06
    Publishing country England
    Document type Journal Article
    ZDB-ID 80075-2
    ISSN 1532-1827 ; 0007-0920
    ISSN (online) 1532-1827
    ISSN 0007-0920
    DOI 10.1038/s41416-024-02671-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

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  2. Article ; Online: Pulmonary nodular lymphoid hyperplasia presenting as cavitating lung mass.

    Alameer, Aqeel / Duraikannu, Chary / Kanodia, Avinash Kumar / Dorward, David

    BMJ case reports

    2023  Volume 16, Issue 8

    Abstract: Pulmonary nodular lymphoid hyperplasia (PNLH) is a rare non-neoplastic disorder, which can mimic malignancy due to its indolent yet progressive nature. Here, we report a case of surgically proven PNLH that progressed over many years from a ground glass ... ...

    Abstract Pulmonary nodular lymphoid hyperplasia (PNLH) is a rare non-neoplastic disorder, which can mimic malignancy due to its indolent yet progressive nature. Here, we report a case of surgically proven PNLH that progressed over many years from a ground glass opacity to a solid cavitating lesion mimicking a slow growing primary lung carcinoma.
    MeSH term(s) Humans ; Hyperplasia/diagnostic imaging ; Hyperplasia/pathology ; Lung Diseases/diagnostic imaging ; Lung Diseases/surgery ; Lung Diseases/pathology ; Lymphoproliferative Disorders/pathology ; Lung/diagnostic imaging ; Lung/pathology
    Language English
    Publishing date 2023-08-10
    Publishing country England
    Document type Case Reports ; Journal Article
    ISSN 1757-790X
    ISSN (online) 1757-790X
    DOI 10.1136/bcr-2022-254121
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  3. Article ; Online: Location of CD39

    Koppensteiner, Lilian / Mathieson, Layla / Pattle, Samuel / Dorward, David A / O'Connor, Richard / Akram, Ahsan R

    Journal for immunotherapy of cancer

    2023  Volume 11, Issue 8

    Abstract: Purpose: An improved mechanistic understanding of immunosuppressive pathways in non-small cell lung cancer (NSCLC) is important to develop novel diagnostic and therapeutic approaches. Here, we investigate the prognostic significance of the ... ...

    Abstract Purpose: An improved mechanistic understanding of immunosuppressive pathways in non-small cell lung cancer (NSCLC) is important to develop novel diagnostic and therapeutic approaches. Here, we investigate the prognostic significance of the ectonucleotidases CD39 and CD73 in NSCLC.
    Experimental design: The expression and localization of CD39, CD73 and CD103 was digitally quantified in a cohort of 162 early treatment naïve NSCLC patients using multiplex-immunofluorescence and related to patient outcome. Expression among different cell-populations was assessed via flow cytometry. Targeted RNA-Seq was performed on CD4
    Results: We demonstrate that flow cytometry of early untreated NSCLC patients shows an upregulation of CD39 expression in the tumor tissue among natural killer (NK) cells, fibroblasts and T cells. CD73 expression is mainly found among fibroblasts and Epcam+cells in the tumor tissue. Multiplex Immunofluorescence in a cohort of 162 early untreated NSCLC patients demonstrates that CD39 expression is mainly localized in the tumor stroma while CD73 expression is equally distributed between tumor nest and stroma, and high expression of CD39 and CD73 in the tumor stroma is associated with poor recurrence-free survival (RFS) at 5 years. Additionally, we find that CD8+T cells located in the tumor nest express CD103 and the density of CD39+CD103+CD8+ T cells in the tumor nest predicts improved RFS at 5 years. Targeted RNA-Seq shows that the tumor microenvironment of NSCLC upregulates regulatory pathways in CD4
    Conclusions: Knowledge of patterns of distribution and location are required to understand the prognostic impact of CD39
    MeSH term(s) Humans ; Carcinoma, Non-Small-Cell Lung ; CD8-Positive T-Lymphocytes ; Lung Neoplasms ; CD4-Positive T-Lymphocytes ; T-Lymphocytes, Cytotoxic ; Tumor Microenvironment
    Language English
    Publishing date 2023-08-30
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2719863-7
    ISSN 2051-1426 ; 2051-1426
    ISSN (online) 2051-1426
    ISSN 2051-1426
    DOI 10.1136/jitc-2023-006770
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Correction to: Assays of Eosinophil Apoptosis and Phagocytic Uptake.

    Gachanja, Naomi N / Dorward, David A / Rossi, Adriano G / Lucas, Christopher D

    Methods in molecular biology (Clifton, N.J.)

    2021  Volume 2241, Page(s) C1

    Language English
    Publishing date 2021-08-26
    Publishing country United States
    Document type Journal Article ; Published Erratum
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-1095-4_22
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  5. Article ; Online: Assays of Eosinophil Apoptosis and Phagocytic Uptake.

    Gachanja, Naomi N / Dorward, David A / Rossi, Adriano G / Lucas, Christopher D

    Methods in molecular biology (Clifton, N.J.)

    2021  Volume 2241, Page(s) 113–132

    Abstract: Eosinophil apoptosis (programmed cell death) plays an important role in several inflammatory and allergic conditions. Apoptosis triggers various mechanisms including activation of cysteine-aspartic proteases (caspases) and is characterized by ... ...

    Abstract Eosinophil apoptosis (programmed cell death) plays an important role in several inflammatory and allergic conditions. Apoptosis triggers various mechanisms including activation of cysteine-aspartic proteases (caspases) and is characterized by morphological and biochemical changes. These include cellular condensation, nuclear fragmentation, increased mitochondrial permeability with loss of membrane potential, and exposure of phosphatidylserine on the cell membrane. A greater understanding of apoptotic mechanisms, subsequent phagocytosis (efferocytosis), and regulation of these processes is critical to understanding disease pathogenesis and development of potential novel therapeutic agents. Release of soluble factors and alterations to surface marker expression by eosinophils undergoing apoptosis aid them in signaling their presence to the immediate environment, and their subsequent recognition by phagocytic cells such as macrophages. Uptake of apoptotic cells usually suppresses inflammation by restricting proinflammatory responses and promoting anti-inflammatory and tissue repair responses. This, in turn, promotes resolution of inflammation. Defects in the apoptotic or efferocytosis mechanisms perpetuate inflammation, resulting in chronic inflammation and enhanced disease severity. This can be due to increased eosinophil life span or cell necrosis characterized by loss of cell membrane integrity and release of toxic intracellular mediators. In this chapter, we detail some of the key assays that are used to assess eosinophil apoptosis, as well as the intracellular signaling pathways involved and phagocytic clearance of these cells.
    MeSH term(s) Annexin A5/chemistry ; Apoptosis/immunology ; Apoptosis/physiology ; Biological Transport ; Caspases/metabolism ; Eosinophils/cytology ; Eosinophils/physiology ; Humans ; Immunohistochemistry/methods ; Inflammation/metabolism ; Macrophages/metabolism ; Membrane Potentials/physiology ; Microscopy/methods ; Microscopy, Electron/methods ; Mitochondria/metabolism ; Phagocytes/metabolism ; Phagocytes/physiology ; Phagocytosis/immunology ; Phagocytosis/physiology ; Propidium/chemistry ; Signal Transduction
    Chemical Substances Annexin A5 ; Propidium (36015-30-2) ; Caspases (EC 3.4.22.-)
    Language English
    Publishing date 2021-08-06
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-1095-4_10
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  6. Article: Fibre-based fluorescence-lifetime imaging microscopy: a real-time biopsy guidance tool for suspected lung cancer.

    Fernandes, Susan / Williams, Elvira / Finlayson, Neil / Stewart, Hazel / Dhaliwal, Catharine / Dorward, David A / Wallace, William A / Akram, Ahsan R / Stone, James / Dhaliwal, Kevin / Williams, Gareth O S

    Translational lung cancer research

    2024  Volume 13, Issue 2, Page(s) 355–361

    Abstract: Lung cancer is the most common cause of cancer-related deaths worldwide. Early detection improves outcomes, however, existing sampling techniques are associated with suboptimal diagnostic yield and procedure-related complications. Autofluorescence-based ... ...

    Abstract Lung cancer is the most common cause of cancer-related deaths worldwide. Early detection improves outcomes, however, existing sampling techniques are associated with suboptimal diagnostic yield and procedure-related complications. Autofluorescence-based fluorescence-lifetime imaging microscopy (FLIM), a technique which measures endogenous fluorophore decay rates, may aid identification of optimal biopsy sites in suspected lung cancer. Our fibre-based fluorescence-lifetime imaging system, utilising 488 nm excitation, which is deliverable via existing diagnostic platforms, enables real-time visualisation and lifetime analysis of distal alveolar lung structure. We evaluated the diagnostic accuracy of the fibre-based fluorescence-lifetime imaging system to detect changes in fluorescence lifetime in freshly resected
    Language English
    Publishing date 2024-02-28
    Publishing country China
    Document type Journal Article
    ZDB-ID 2754335-3
    ISSN 2226-4477 ; 2218-6751
    ISSN (online) 2226-4477
    ISSN 2218-6751
    DOI 10.21037/tlcr-23-638
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  7. Article ; Online: Immunohistochemistry for small-cell carcinoma: a potential diagnostic pitfall.

    Wallace, William A / Dorward, David A / Salter, Donald M

    Histopathology

    2019  Volume 74, Issue 5, Page(s) 792–794

    MeSH term(s) Aged ; Aged, 80 and over ; Biomarkers, Tumor ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; Lung Neoplasms/diagnosis ; Lung Neoplasms/metabolism ; Lung Neoplasms/pathology ; Male ; Small Cell Lung Carcinoma/diagnosis ; Small Cell Lung Carcinoma/metabolism ; Small Cell Lung Carcinoma/pathology
    Chemical Substances Biomarkers, Tumor
    Language English
    Publishing date 2019-01-28
    Publishing country England
    Document type Case Reports ; Journal Article
    ZDB-ID 131914-0
    ISSN 1365-2559 ; 0309-0167
    ISSN (online) 1365-2559
    ISSN 0309-0167
    DOI 10.1111/his.13789
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1328: Show issues Location:
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    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  8. Article ; Online: Storylines of family medicine VI: ways of being-in the office with patients.

    Ventres, William B / Stone, Leslie A / LaVallee, Lisa A / Loxterkamp, David / Brown, Jonisha R / Waxman, Dael M / Dorward, Peter S / Cawse-Lucas, Jeanne / Mauksch, Larry B / Kieber-Emmons, Autumn M / Crabtree, Benjamin F / Miller, William L / Brohm, Veronica M / Daaleman, Timothy P / Bossenbroek Fedoriw, Kelly

    Family medicine and community health

    2024  Volume 12, Issue Suppl 3

    Abstract: Storylines of Family ... ...

    Abstract Storylines of Family Medicine
    MeSH term(s) Humans ; Family Practice ; Physicians, Family ; Drama ; Metaphor ; Patient-Centered Care
    Language English
    Publishing date 2024-04-12
    Publishing country England
    Document type Journal Article
    ZDB-ID 2986753-8
    ISSN 2009-8774 ; 2305-6983
    ISSN (online) 2009-8774
    ISSN 2305-6983
    DOI 10.1136/fmch-2024-002793
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  9. Article ; Online: Epithelial Cells and Inflammation in Pulmonary Wound Repair.

    Croasdell Lucchini, Amanda / Gachanja, Naomi N / Rossi, Adriano G / Dorward, David A / Lucas, Christopher D

    Cells

    2021  Volume 10, Issue 2

    Abstract: Respiratory diseases are frequently characterised by epithelial injury, airway inflammation, defective tissue repair, and airway remodelling. This may occur in a subacute or chronic context, such as asthma and chronic obstructive pulmonary disease, or ... ...

    Abstract Respiratory diseases are frequently characterised by epithelial injury, airway inflammation, defective tissue repair, and airway remodelling. This may occur in a subacute or chronic context, such as asthma and chronic obstructive pulmonary disease, or occur acutely as in pathogen challenge and acute respiratory distress syndrome (ARDS). Despite the frequent challenge of lung homeostasis, not all pulmonary insults lead to disease. Traditionally thought of as a quiescent organ, emerging evidence highlights that the lung has significant capacity to respond to injury by repairing and replacing damaged cells. This occurs with the appropriate and timely resolution of inflammation and concurrent initiation of tissue repair programmes. Airway epithelial cells are key effectors in lung homeostasis and host defence; continual exposure to pathogens, toxins, and particulate matter challenge homeostasis, requiring robust defence and repair mechanisms. As such, the epithelium is critically involved in the return to homeostasis, orchestrating the resolution of inflammation and initiating tissue repair. This review examines the pivotal role of pulmonary airway epithelial cells in initiating and moderating tissue repair and restitution. We discuss emerging evidence of the interactions between airway epithelial cells and candidate stem or progenitor cells to initiate tissue repair as well as with cells of the innate and adaptive immune systems in driving successful tissue regeneration. Understanding the mechanisms of intercellular communication is rapidly increasing, and a major focus of this review includes the various mediators involved, including growth factors, extracellular vesicles, soluble lipid mediators, cytokines, and chemokines. Understanding these areas will ultimately identify potential cells, mediators, and interactions for therapeutic targeting.
    MeSH term(s) Epithelial Cells/metabolism ; Humans ; Inflammation/metabolism ; Lung Injury/therapy ; Wound Healing
    Language English
    Publishing date 2021-02-05
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells10020339
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  10. Article: Phototherapeutic Induction of Immunogenic Cell Death and CD8+ T Cell-Granzyme B Mediated Cytolysis in Human Lung Cancer Cells and Organoids.

    Valančiūtė, Asta / Mathieson, Layla / O'Connor, Richard A / Scott, Jamie I / Vendrell, Marc / Dorward, David A / Akram, Ahsan R / Dhaliwal, Kevin

    Cancers

    2022  Volume 14, Issue 17

    Abstract: Augmenting T cell mediated tumor killing via immunogenic cancer cell death (ICD) is the cornerstone of emerging immunotherapeutic approaches. We investigated the potential of methylene blue photodynamic therapy (MB-PDT) to induce ICD in human lung cancer. ...

    Abstract Augmenting T cell mediated tumor killing via immunogenic cancer cell death (ICD) is the cornerstone of emerging immunotherapeutic approaches. We investigated the potential of methylene blue photodynamic therapy (MB-PDT) to induce ICD in human lung cancer. Non-Small Cell Lung Cancer (NSCLC) cell lines and primary human lung cancer organoids were evaluated in co-culture killing assays with MB-PDT and light emitting diodes (LEDs). ICD was characterised using immunoblotting, immunofluorescence, flow cytometry and confocal microscopy. Phototherapy with MB treatment and low energy LEDs decreased the proliferation of NSCLC cell lines inducing early necrosis associated with reduced expression of the anti-apoptotic protein, Bcl2 and increased expression of ICD markers, calreticulin (CRT), intercellular cell-adhesion molecule-1 (ICAM-1) and major histocompatibility complex I (MHC-I) in NSCLC cells. MB-PDT also potentiated CD8
    Language English
    Publishing date 2022-08-25
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers14174119
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