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  1. Article ; Online: A mucin degrader for cancer therapy.

    Beatson, Richard / Burchell, Joy M

    Nature biotechnology

    2023  Volume 42, Issue 4, Page(s) 572–573

    MeSH term(s) Humans ; Mucins ; Neoplasms/drug therapy
    Chemical Substances Mucins
    Language English
    Publishing date 2023-10-07
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1311932-1
    ISSN 1546-1696 ; 1087-0156
    ISSN (online) 1546-1696
    ISSN 1087-0156
    DOI 10.1038/s41587-023-01984-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2167: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (1.OG)
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    Zs.MO 137: Show issues
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  2. Article ; Online: CAR T-Cell Targeting of Macrophage Colony-Stimulating Factor Receptor.

    Achkova, Daniela Yordanova / Beatson, Richard Esmond / Maher, John

    Cells

    2022  Volume 11, Issue 14

    Abstract: Macrophage colony-stimulating factor receptor (M-CSFR) is found in cells of the mononuclear phagocyte lineage and is aberrantly expressed in a range of tumours, in addition to tumour-associated macrophages. Consequently, a variety of cancer therapies ... ...

    Abstract Macrophage colony-stimulating factor receptor (M-CSFR) is found in cells of the mononuclear phagocyte lineage and is aberrantly expressed in a range of tumours, in addition to tumour-associated macrophages. Consequently, a variety of cancer therapies directed against M-CSFR are under development. We set out to engineer chimeric antigen receptors (CARs) that employ the natural ligands of this receptor, namely M-CSF or interleukin (IL)-34, to achieve specificity for M-CSFR-expressing target cells. Both M-CSF and IL-34 bind to overlapping regions of M-CSFR, although affinity of IL-34 is significantly greater than that of M-CSF. Matched second- and third-generation CARs targeted using M-CSF or IL-34 were expressed in human T-cells using the SFG retroviral vector. We found that both M-CSF- and IL-34-containing CARs enable T-cells to mediate selective destruction of tumour cells that express enforced or endogenous M-CSFR, accompanied by production of both IL-2 and interferon (IFN)-γ. Although they contain an additional co-stimulatory module, third-generation CARs did not outperform second-generation CARs. M-CSF-containing CARs mediated enhanced cytokine production and cytolytic activity compared to IL-34-containing CARs. These data demonstrate the feasibility of targeting M-CSFR using ligand-based CARs and raise the possibility that the low picomolar affinity of IL-34 for M-CSFR is detrimental to CAR function.
    MeSH term(s) Gene Expression ; Humans ; Immunotherapy, Adoptive/methods ; Macrophage Colony-Stimulating Factor/metabolism ; Receptor, Macrophage Colony-Stimulating Factor/metabolism ; Receptors, Chimeric Antigen/genetics ; Receptors, Chimeric Antigen/metabolism ; T-Lymphocytes/metabolism
    Chemical Substances Receptors, Chimeric Antigen ; Macrophage Colony-Stimulating Factor (81627-83-0) ; Receptor, Macrophage Colony-Stimulating Factor (EC 2.7.10.1)
    Language English
    Publishing date 2022-07-13
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells11142190
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Editorial: Glycans: Masters of immunity, from cancers to inflammatory disease.

    Beatson, Richard / Läubli, Heinz / Pearce, Oliver M T / Reis, Celso A

    Frontiers in immunology

    2022  Volume 13, Page(s) 1002679

    MeSH term(s) Humans ; Neoplasms ; Polysaccharides
    Chemical Substances Polysaccharides
    Language English
    Publishing date 2022-08-17
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2022.1002679
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Editorial: Precision medical approach-driven multi-dimensional diagnosis and treatment strategies.

    Beatson, Richard / Chu, Cong-Qiu / Yu, Su Jong / Liu, Xiaolong / Zhao, Jie

    Frontiers in medicine

    2023  Volume 10, Page(s) 1164830

    Language English
    Publishing date 2023-03-21
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2775999-4
    ISSN 2296-858X
    ISSN 2296-858X
    DOI 10.3389/fmed.2023.1164830
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Harnessing CD8

    Ceeraz, Sabrina / Thompson, Charlotte R / Beatson, Richard / Choy, Ernest H

    Cells

    2021  Volume 10, Issue 11

    Abstract: T regulatory cell therapy presents a novel therapeutic strategy for patients with autoimmune diseases or who are undergoing transplantation. At present, the ... ...

    Abstract T regulatory cell therapy presents a novel therapeutic strategy for patients with autoimmune diseases or who are undergoing transplantation. At present, the CD4
    MeSH term(s) Animals ; Autoimmune Diseases/immunology ; Autoimmune Diseases/therapy ; CD28 Antigens/metabolism ; CD8-Positive T-Lymphocytes/immunology ; Humans ; Immunosuppression Therapy ; Immunotherapy, Adoptive ; T-Lymphocytes, Regulatory/immunology
    Chemical Substances CD28 Antigens
    Language English
    Publishing date 2021-11-01
    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/cells10112973
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Apoptosis in the Pancreatic Cancer Tumor Microenvironment-The Double-Edged Sword of Cancer-Associated Fibroblasts.

    Pfeifer, Ester / Burchell, Joy M / Dazzi, Francesco / Sarker, Debashis / Beatson, Richard

    Cells

    2021  Volume 10, Issue 7

    Abstract: Pancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis. This is attributed to the disease already being advanced at presentation and having a particularly aggressive tumor biology. The PDAC tumor microenvironment (TME) is characterized ...

    Abstract Pancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis. This is attributed to the disease already being advanced at presentation and having a particularly aggressive tumor biology. The PDAC tumor microenvironment (TME) is characterized by a dense desmoplastic stroma, dominated by cancer-associated fibroblasts (CAF), extracellular matrix (ECM) and immune cells displaying immunosuppressive phenotypes. Due to the advanced stage at diagnosis, the depletion of immune effector cells and lack of actionable genomic targets, the standard treatment is still apoptosis-inducing regimens such as chemotherapy. Paradoxically, it has emerged that the direct induction of apoptosis of cancer cells may fuel oncogenic processes in the TME, including education of CAF and immune cells towards pro-tumorigenic phenotypes. The direct effect of cytotoxic therapies on CAF may also enhance tumorigenesis. With the awareness that CAF are the predominant cell type in PDAC driving tumorigenesis with various tumor supportive functions, efforts have been made to try to target them. However, efforts to target CAF have, to date, shown disappointing results in clinical trials. With the help of sophisticated single cell analyses it is now appreciated that CAF in PDAC are a heterogenous population with both tumor supportive and tumor suppressive functions. Hence, there remains a debate whether targeting CAF in PDAC is a valid therapeutic strategy. In this review we discuss how cytotoxic therapies and the induction of apoptosis in PDAC fuels oncogenesis by the education of surrounding stromal cells, with a particular focus on the potential pro-tumorigenic outcomes arising from targeting CAF. In addition, we explore therapeutic avenues to potentially avoid the oncogenic effects of apoptosis in PDAC CAF.
    MeSH term(s) Apoptosis ; Cancer-Associated Fibroblasts/pathology ; Carcinogenesis/pathology ; Humans ; Models, Biological ; Pancreatic Neoplasms/pathology ; Tumor Microenvironment
    Language English
    Publishing date 2021-07-01
    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/cells10071653
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  7. Article ; Online: Generation and application of TGFβ-educated human Vγ9Vδ2 T cells.

    Parente-Pereira, Ana C / Beatson, Richard E / Davies, David M / Hull, Caroline / Whilding, Lynsey M / Porter, Joanna C / Maher, John

    STAR protocols

    2022  Volume 3, Issue 2, Page(s) 101319

    Abstract: Clinical trials that tested the antitumor activity of γδ T cells have been mostly unsuccessful. To address this, we expanded human Vγ9Vδ2 T cells in TGFβ1, a cytokine which enhances their viability, trafficking properties, and intrinsic antitumor ... ...

    Abstract Clinical trials that tested the antitumor activity of γδ T cells have been mostly unsuccessful. To address this, we expanded human Vγ9Vδ2 T cells in TGFβ1, a cytokine which enhances their viability, trafficking properties, and intrinsic antitumor activity. This protocol summarizes the production and
    MeSH term(s) Animals ; Cytokines ; Humans ; Mice ; Receptors, Chimeric Antigen ; T-Lymphocytes ; Transforming Growth Factor beta
    Chemical Substances Cytokines ; Receptors, Chimeric Antigen ; Transforming Growth Factor beta
    Language English
    Publishing date 2022-04-18
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2666-1667
    ISSN (online) 2666-1667
    DOI 10.1016/j.xpro.2022.101319
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  8. Article: Integrative pharmacogenomics revealed three subtypes with different immune landscapes and specific therapeutic responses in lung adenocarcinoma

    Ge, Xiaoyong / Liu, Zaoqu / Weng, Siyuan / Xu, Hui / Zhang, Yuyuan / Liu, Long / Dang, Qin / Guo, Chunguang / Beatson, Richard / Deng, Jinhai / Han, Xinwei

    Computational and Structural Biotechnology Journal. 2022, v. 20

    2022  

    Abstract: Pharmacogenomics is crucial for individualized drug therapy and plays an increasingly vital role in precision medicine decision-making. However, pharmacogenomics-based molecular subtypes and their potential clinical significance remain primarily ... ...

    Abstract Pharmacogenomics is crucial for individualized drug therapy and plays an increasingly vital role in precision medicine decision-making. However, pharmacogenomics-based molecular subtypes and their potential clinical significance remain primarily unexplored in lung adenocarcinoma (LUAD). A total of 2065 samples were recruited from eight independent cohorts. Pharmacogenomics data were generated from the profiling of relative inhibition simultaneously in mixtures (PRISM) and the genomics of drug sensitivity in cancer (GDSC) databases. Multiple bioinformatics approaches were performed to identify pharmacogenomics-based subtypes and find subtype-specific properties. Three reproducible molecular subtypes were found, which were independent prognostic factors and highly associated with stage, survival status, and accepted molecular subtypes. Pharmacogenomics-based subtypes had distinct molecular characteristics: S-Ⅰ was inflammatory, proliferative, and immune-evasion; S-Ⅱ was proliferative and genetics-driven; S-III was metabolic and methylation-driven. Finally, our study provided subtype-guided personalized treatment strategies: Immune checkpoint blockers (ICBs), doxorubicin, tipifarnib, AZ628, and AZD6244 were for S-Ⅰ; Cisplatin, camptothecin, roscovitine, and A.443654 were for S-Ⅱ; Docetaxel, paclitaxel, vinorelbine, and BIBW2992 were for S-III. We provided a novel molecular classification strategy and revealed three pharmacogenomics-based subtypes for LUAD patients, which uncovered potential subtype-related and patient-specific therapeutic strategies.
    Keywords adenocarcinoma ; bioinformatics ; biotechnology ; cisplatin ; decision making ; doxorubicin ; drug therapy ; immune evasion ; lungs ; paclitaxel ; pharmacogenomics ; precision medicine
    Language English
    Size p. 3449-3460.
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 2694435-2
    ISSN 2001-0370
    ISSN 2001-0370
    DOI 10.1016/j.csbj.2022.06.064
    Database NAL-Catalogue (AGRICOLA)

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  9. Article: Mucins and their receptors in chronic lung disease.

    Denneny, Emma / Sahota, Jagdeep / Beatson, Richard / Thornton, David / Burchell, Joy / Porter, Joanna

    Clinical & translational immunology

    2020  Volume 9, Issue 3, Page(s) e01120

    Abstract: There is growing recognition that mucus and mucin biology have a considerable impact on respiratory health, and subsequent global morbidity and mortality. Mucins play a critical role in chronic lung disease, not only by providing a physical barrier and ... ...

    Abstract There is growing recognition that mucus and mucin biology have a considerable impact on respiratory health, and subsequent global morbidity and mortality. Mucins play a critical role in chronic lung disease, not only by providing a physical barrier and clearing pathogens, but also in immune homeostasis. The aim of this review is to familiarise the reader with the role of mucins in both lung health and disease, with particular focus on function in immunity, infection and inflammation. We will also discuss their receptors, termed glycan-binding proteins, and how they provide an attractive prospect for therapeutic intervention.
    Language English
    Publishing date 2020-03-17
    Publishing country Australia
    Document type Journal Article
    ZDB-ID 2694482-0
    ISSN 2050-0068
    ISSN 2050-0068
    DOI 10.1002/cti2.1120
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: The role of TXNIP in cancer: a fine balance between redox, metabolic, and immunological tumor control.

    Deng, Jinhai / Pan, Teng / Liu, Zaoqu / McCarthy, Caitlin / Vicencio, Jose M / Cao, Lulu / Alfano, Giovanna / Suwaidan, Ali Abdulnabi / Yin, Mingzhu / Beatson, Richard / Ng, Tony

    British journal of cancer

    2023  Volume 129, Issue 12, Page(s) 1877–1892

    Abstract: Thioredoxin-interacting protein (TXNIP) is commonly considered a master regulator of cellular oxidation, regulating the expression and function of Thioredoxin (Trx). Recent work has identified that TXNIP has a far wider range of additional roles: from ... ...

    Abstract Thioredoxin-interacting protein (TXNIP) is commonly considered a master regulator of cellular oxidation, regulating the expression and function of Thioredoxin (Trx). Recent work has identified that TXNIP has a far wider range of additional roles: from regulating glucose and lipid metabolism, to cell cycle arrest and inflammation. Its expression is increased by stressors commonly found in neoplastic cells and the wider tumor microenvironment (TME), and, as such, TXNIP has been extensively studied in cancers. In this review, we evaluate the current literature regarding the regulation and the function of TXNIP, highlighting its emerging role in modulating signaling between different cell types within the TME. We then assess current and future translational opportunities and the associated challenges in this area. An improved understanding of the functions and mechanisms of TXNIP in cancers may enhance its suitability as a therapeutic target.
    MeSH term(s) Humans ; Carrier Proteins/genetics ; Carrier Proteins/metabolism ; Glucose ; Inflammation ; Neoplasms/immunology ; Neoplasms/metabolism ; Oxidation-Reduction ; Thioredoxins/metabolism ; Tumor Microenvironment
    Chemical Substances Carrier Proteins ; Glucose (IY9XDZ35W2) ; Thioredoxins (52500-60-4) ; TXNIP protein, human
    Language English
    Publishing date 2023-10-04
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 80075-2
    ISSN 1532-1827 ; 0007-0920
    ISSN (online) 1532-1827
    ISSN 0007-0920
    DOI 10.1038/s41416-023-02442-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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