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  1. AU="Bayliss, Richard"
  2. AU="González-Enseñat, Maria Antònia"
  3. AU=Camara Amadou K S
  4. AU="Luginbuehl, Helena"
  5. AU="Irani, Zubin A"
  6. AU="Santos, H"
  7. AU="Villota-Rivas, Marcela"
  8. AU="Sepe, Thomas"
  9. AU="Prasad, Aman"
  10. AU="Bortz, Cole"
  11. AU="Clarke, Julia R"
  12. AU=Jordan William D Jr
  13. AU="Frangaj, Brulinda"
  14. AU="Oostindjer, Andrew"
  15. AU="Diarra, Zoumana"
  16. AU="Saragoni, V G"

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Treffer 1 - 10 von insgesamt 124

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  1. Artikel: A Less Accurate History of Babinski.

    Bayliss, Richard

    Journal of the Royal College of Physicians of London

    2019  Band 30, Heft 2, Seite(n) 189–190

    Sprache Englisch
    Erscheinungsdatum 2019-01-22
    Erscheinungsland England
    Dokumenttyp Journal Article ; Comment
    ZDB-ID 3005-3
    ISSN 0035-8819
    ISSN 0035-8819
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: EML4-ALK biology and drug resistance in non-small cell lung cancer: a new phase of discoveries.

    Elshatlawy, Mariam / Sampson, Josephina / Clarke, Katy / Bayliss, Richard

    Molecular oncology

    2023  Band 17, Heft 6, Seite(n) 950–963

    Abstract: Anaplastic lymphoma kinase (ALK) can be driven to oncogenic activity by different types of mutational events such as point-mutations, for example F1174L in neuroblastoma, and gene fusions, for example with echinoderm microtubule-associated protein-like 4 ...

    Abstract Anaplastic lymphoma kinase (ALK) can be driven to oncogenic activity by different types of mutational events such as point-mutations, for example F1174L in neuroblastoma, and gene fusions, for example with echinoderm microtubule-associated protein-like 4 (EML4) in non-small cell lung cancer (NSCLC). EML4-ALK variants result from different breakpoints, generating fusions of different sizes and properties. The most common variants (Variant 1 and Variant 3) form cellular compartments with distinct physical properties. The presence of a partial, probably misfolded beta-propeller domain in variant 1 confers solid-like properties to the compartments it forms, greater dependence on Hsp90 for protein stability and higher cell sensitivity to ALK tyrosine kinase inhibitors (TKIs). These differences translate to the clinic because variant 3, on average, worsens patient prognosis and increases metastatic risk. Latest generation ALK-TKIs are beneficial for most patients with EML4-ALK fusions. However, resistance to ALK inhibitors can occur via point-mutations within the kinase domain of the EML4-ALK fusion, for example G1202R, reducing inhibitor effectiveness. Here, we discuss the biology of EML4-ALK variants, their impact on treatment response, ALK-TKI drug resistance mechanisms and potential combination therapies.
    Mesh-Begriff(e) Humans ; Anaplastic Lymphoma Kinase/genetics ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/genetics ; Carcinoma, Non-Small-Cell Lung/metabolism ; Cytoskeletal Proteins ; Drug Resistance, Neoplasm/genetics ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics ; Lung Neoplasms/pathology ; Oncogene Proteins, Fusion/genetics ; Oncogene Proteins, Fusion/metabolism ; Protein Kinase Inhibitors/pharmacology ; Protein Kinase Inhibitors/therapeutic use ; Protein-Tyrosine Kinases
    Chemische Substanzen Anaplastic Lymphoma Kinase (EC 2.7.10.1) ; Cytoskeletal Proteins ; EML4-ALK fusion protein, human ; Oncogene Proteins, Fusion ; Protein Kinase Inhibitors ; Protein-Tyrosine Kinases (EC 2.7.10.1) ; EML4 protein, human (EC 3.4.21.-)
    Sprache Englisch
    Erscheinungsdatum 2023-05-15
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Review
    ZDB-ID 2415106-3
    ISSN 1878-0261 ; 1574-7891
    ISSN (online) 1878-0261
    ISSN 1574-7891
    DOI 10.1002/1878-0261.13446
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: ALKing the flames of lung cancer immunosensitivity.

    Bayliss, Richard / Sarnowska, Elżbieta / Yeoh, Sharon / Sampson, Josephina

    Molecular oncology

    2023  Band 17, Heft 11, Seite(n) 2218–2220

    Abstract: Immune checkpoint inhibitors (ICIs) are utilised in treating non-small cell lung cancer (NSCLC) by enhancing the immune response against cancer cells. However, they are not effective against cancers with certain genetic alterations. A recent study by ... ...

    Abstract Immune checkpoint inhibitors (ICIs) are utilised in treating non-small cell lung cancer (NSCLC) by enhancing the immune response against cancer cells. However, they are not effective against cancers with certain genetic alterations. A recent study by Mota et al. focussed on understanding why ALK+ NSCLC cancers are immune cold and making them more receptive to ICIs using a vaccine-based approach. The study highlighted cell-specific differences in the presentation of immunogenic peptides and the location of tumours as factors in the poor immune response. Vaccines based on ALK peptides improved immune response, and when combined with ICIs, this led to a striking improvement in survival in a mouse model of ALK+ NSCLC.
    Mesh-Begriff(e) Mice ; Animals ; Lung Neoplasms/genetics ; Carcinoma, Non-Small-Cell Lung/genetics ; B7-H1 Antigen ; Receptor Protein-Tyrosine Kinases ; Peptides
    Chemische Substanzen B7-H1 Antigen ; Receptor Protein-Tyrosine Kinases (EC 2.7.10.1) ; Peptides
    Sprache Englisch
    Erscheinungsdatum 2023-10-12
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 2415106-3
    ISSN 1878-0261 ; 1574-7891
    ISSN (online) 1878-0261
    ISSN 1574-7891
    DOI 10.1002/1878-0261.13533
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel: HER3 overexpression: a predictive marker for poor prognosis in advanced ALK-positive non-small cell lung cancer treated with ALK inhibitors.

    Kim, Meejeong / Ju, Hyun-Min / Song, Ji-Young / Sampson, Josephina / Bayliss, Richard / Choi, Jene

    Translational lung cancer research

    2024  Band 13, Heft 2, Seite(n) 321–333

    Abstract: Background: Anaplastic lymphoma kinase (ALK)-targeted tyrosine kinase inhibitors (TKIs) improve patient survival; however, some patients develop ALK-TKI resistance with unidentified mechanisms. We investigated ErbB family and c-MET expression in ... ...

    Abstract Background: Anaplastic lymphoma kinase (ALK)-targeted tyrosine kinase inhibitors (TKIs) improve patient survival; however, some patients develop ALK-TKI resistance with unidentified mechanisms. We investigated ErbB family and c-MET expression in patients with ALK-positive non-small cell lung cancer (NSCLC) to understand their roles in the ALK-TKI response.
    Methods: We studied 72 patients with advanced ALK-positive NSCLC with
    Results: High expression of c-MET, EGFR, HER2, and HER3 was observed in 4.9%, 18.0%, 1.6%, and 25.8% of primary tumors, respectively, and 18.5%, 37.0%, 10.7%, and 35.7% of secondary tumors, respectively. HER3 overexpression in primary tumors showed inferior survival (P=0.132). In the subgroup with
    Conclusions: HER3 overexpression has potential as a prognostic marker in ALK-positive NSCLCs, including ALK-TKI naïve and treated cases, especially those with
    Sprache Englisch
    Erscheinungsdatum 2024-02-28
    Erscheinungsland China
    Dokumenttyp Journal Article
    ZDB-ID 2754335-3
    ISSN 2226-4477 ; 2218-6751
    ISSN (online) 2226-4477
    ISSN 2218-6751
    DOI 10.21037/tlcr-23-804
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  5. Artikel ; Online: Structural features of the protein kinase domain and targeted binding by small-molecule inhibitors.

    Arter, Chris / Trask, Luke / Ward, Sarah / Yeoh, Sharon / Bayliss, Richard

    The Journal of biological chemistry

    2022  Band 298, Heft 8, Seite(n) 102247

    Abstract: Protein kinases are key components in cellular signaling pathways as they carry out the phosphorylation of proteins, primarily on Ser, Thr, and Tyr residues. The catalytic activity of protein kinases is regulated, and they can be thought of as molecular ... ...

    Abstract Protein kinases are key components in cellular signaling pathways as they carry out the phosphorylation of proteins, primarily on Ser, Thr, and Tyr residues. The catalytic activity of protein kinases is regulated, and they can be thought of as molecular switches that are controlled through protein-protein interactions and post-translational modifications. Protein kinases exhibit diverse structural mechanisms of regulation and have been fascinating subjects for structural biologists from the first crystal structure of a protein kinase over 30 years ago, to recent insights into kinase assemblies enabled by the breakthroughs in cryo-EM. Protein kinases are high-priority targets for drug discovery in oncology and other disease settings, and kinase inhibitors have transformed the outcomes of specific groups of patients. Most kinase inhibitors are ATP competitive, deriving potency by occupying the deep hydrophobic pocket at the heart of the kinase domain. Selectivity of inhibitors depends on exploiting differences between the amino acids that line the ATP site and exploring the surrounding pockets that are present in inactive states of the kinase. More recently, allosteric pockets outside the ATP site are being targeted to achieve high selectivity and to overcome resistance to current therapeutics. Here, we review the key regulatory features of the protein kinase family, describe the different types of kinase inhibitors, and highlight examples where the understanding of kinase regulatory mechanisms has gone hand in hand with the development of inhibitors.
    Mesh-Begriff(e) Adenosine Triphosphate/chemistry ; Drug Discovery ; Humans ; Phosphorylation ; Protein Binding ; Protein Kinase Inhibitors/chemistry ; Protein Kinase Inhibitors/pharmacology ; Protein Kinases/chemistry
    Chemische Substanzen Protein Kinase Inhibitors ; Adenosine Triphosphate (8L70Q75FXE) ; Protein Kinases (EC 2.7.-)
    Sprache Englisch
    Erscheinungsdatum 2022-07-10
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1016/j.jbc.2022.102247
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  6. Artikel ; Online: α-Helix stabilization by co-operative side chain charge-reinforced interactions to phosphoserine in a basic kinase-substrate motif.

    Batchelor, Matthew / Dawber, Robert S / Wilson, Andrew J / Bayliss, Richard

    The Biochemical journal

    2022  Band 479, Heft 5, Seite(n) 687–700

    Abstract: How cellular functions are regulated through protein phosphorylation events that promote or inhibit protein-protein interactions (PPIs) is key to understanding regulatory molecular mechanisms. Whilst phosphorylation can orthosterically or allosterically ... ...

    Abstract How cellular functions are regulated through protein phosphorylation events that promote or inhibit protein-protein interactions (PPIs) is key to understanding regulatory molecular mechanisms. Whilst phosphorylation can orthosterically or allosterically influence protein recognition, phospho-driven changes in the conformation of recognition motifs are less well explored. We recently discovered that clathrin heavy chain recognizes phosphorylated TACC3 through a helical motif that, in the unphosphorylated protein, is disordered. However, it was unclear whether and how phosphorylation could stabilize a helix in a broader context. In the current manuscript, we address this challenge using poly-Ala-based model peptides and a suite of circular dichroism and nuclear magnetic resonance spectroscopies. We show that phosphorylation of a Ser residue stabilizes the α-helix in the context of an Arg(i-3)pSeri Lys(i+4) triad through charge-reinforced side chain interactions with positive co-operativity, whilst phosphorylation of Thr induces an opposing response. This is significant as it may represent a general method for control of PPIs by phosphorylation; basic kinase-substrate motifs are common with 55 human protein kinases recognizing an Arg at a position -3 from the phosphorylated Ser, whilst the Arg(i-3)Seri Lys(i+4) is a motif found in over 2000 human proteins.
    Mesh-Begriff(e) Cell Cycle Proteins ; Circular Dichroism ; Humans ; Microtubule-Associated Proteins ; Phosphorylation ; Phosphoserine ; Protein Conformation, alpha-Helical
    Chemische Substanzen Cell Cycle Proteins ; Microtubule-Associated Proteins ; TACC3 protein, human ; Phosphoserine (17885-08-4)
    Sprache Englisch
    Erscheinungsdatum 2022-02-24
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2969-5
    ISSN 1470-8728 ; 0006-2936 ; 0306-3275 ; 0264-6021
    ISSN (online) 1470-8728
    ISSN 0006-2936 ; 0306-3275 ; 0264-6021
    DOI 10.1042/BCJ20210812
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  7. Artikel: The journey of Zika to the developing brain

    Rombi, Francesca / Bayliss, Richard / Tuplin, Andrew / Yeoh, Sharon

    Molecular biology reports. 2020 Apr., v. 47, no. 4

    2020  

    Abstract: Zika virus is a mosquito-borne Flavivirus originally isolated from humans in 1952. Following its re-emergence in Brazil in 2015, an increase in the number of babies born with microcephaly to infected mothers was observed. Microcephaly is a ... ...

    Abstract Zika virus is a mosquito-borne Flavivirus originally isolated from humans in 1952. Following its re-emergence in Brazil in 2015, an increase in the number of babies born with microcephaly to infected mothers was observed. Microcephaly is a neurodevelopmental disorder, characterised phenotypically by a smaller than average head size, and is usually developed in utero. The 2015 outbreak in the Americas led to the World Health Organisation declaring Zika a Public Health Emergency of International Concern. Since then, much research into the effects of Zika has been carried out. Studies have investigated the structure of the virus, its effects on and evasion of the immune response, cellular entry including target receptors, its transmission from infected mother to foetus and its cellular targets. This review discusses current knowledge and novel research into these areas, in hope of developing a further understanding of how exposure of pregnant women to the Zika virus can lead to impaired brain development of their foetus. Although no longer considered an epidemic in the Americas, the mechanism by which Zika acts is still not comprehensively and wholly understood, and this understanding will be crucial in developing effective vaccines and treatments.
    Schlagwörter World Health Organization ; Zika virus ; brain ; fetus ; head ; immune response ; molecular biology ; public health ; viruses ; Brazil
    Sprache Englisch
    Erscheinungsverlauf 2020-04
    Umfang p. 3097-3115.
    Erscheinungsort Springer Netherlands
    Dokumenttyp Artikel
    Anmerkung NAL-AP-2-clean ; Review
    ZDB-ID 186544-4
    ISSN 1573-4978 ; 0301-4851
    ISSN (online) 1573-4978
    ISSN 0301-4851
    DOI 10.1007/s11033-020-05349-y
    Datenquelle NAL Katalog (AGRICOLA)

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  8. Artikel ; Online: New tools for evaluating protein tyrosine sulfation and carbohydrate sulfation.

    Yeoh, Sharon / Bayliss, Richard

    The Biochemical journal

    2018  Band 475, Heft 19, Seite(n) 3035–3037

    Abstract: Sulfation is a common modification of extracelluar glycans and tyrosine residues on proteins, which is important in many signalling pathways and interactions. Existing methods for studying sulfotransferases, the enzymes that catalyse sulfation, are ... ...

    Abstract Sulfation is a common modification of extracelluar glycans and tyrosine residues on proteins, which is important in many signalling pathways and interactions. Existing methods for studying sulfotransferases, the enzymes that catalyse sulfation, are cumbersome and low-throughput. Recent studies published in the
    Mesh-Begriff(e) Animals ; Carbohydrates/analysis ; Humans ; Nuclear Magnetic Resonance, Biomolecular/methods ; Sulfotransferases/analysis ; Sulfotransferases/metabolism ; Tyrosine/analysis ; Tyrosine/metabolism
    Chemische Substanzen Carbohydrates ; Tyrosine (42HK56048U) ; Sulfotransferases (EC 2.8.2.-) ; heparan-sulfate 2-sulfotransferase (EC 2.8.2.-) ; protein-tyrosine sulfotransferase (EC 2.8.2.20)
    Sprache Englisch
    Erscheinungsdatum 2018-10-05
    Erscheinungsland England
    Dokumenttyp Journal Article ; Review
    ZDB-ID 2969-5
    ISSN 1470-8728 ; 0006-2936 ; 0306-3275 ; 0264-6021
    ISSN (online) 1470-8728
    ISSN 0006-2936 ; 0306-3275 ; 0264-6021
    DOI 10.1042/BCJ20180480
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  9. Artikel ; Online: The journey of Zika to the developing brain.

    Rombi, Francesca / Bayliss, Richard / Tuplin, Andrew / Yeoh, Sharon

    Molecular biology reports

    2020  Band 47, Heft 4, Seite(n) 3097–3115

    Abstract: Zika virus is a mosquito-borne Flavivirus originally isolated from humans in 1952. Following its re-emergence in Brazil in 2015, an increase in the number of babies born with microcephaly to infected mothers was observed. Microcephaly is a ... ...

    Abstract Zika virus is a mosquito-borne Flavivirus originally isolated from humans in 1952. Following its re-emergence in Brazil in 2015, an increase in the number of babies born with microcephaly to infected mothers was observed. Microcephaly is a neurodevelopmental disorder, characterised phenotypically by a smaller than average head size, and is usually developed in utero. The 2015 outbreak in the Americas led to the World Health Organisation declaring Zika a Public Health Emergency of International Concern. Since then, much research into the effects of Zika has been carried out. Studies have investigated the structure of the virus, its effects on and evasion of the immune response, cellular entry including target receptors, its transmission from infected mother to foetus and its cellular targets. This review discusses current knowledge and novel research into these areas, in hope of developing a further understanding of how exposure of pregnant women to the Zika virus can lead to impaired brain development of their foetus. Although no longer considered an epidemic in the Americas, the mechanism by which Zika acts is still not comprehensively and wholly understood, and this understanding will be crucial in developing effective vaccines and treatments.
    Mesh-Begriff(e) Brain/embryology ; Brain/virology ; Brazil/epidemiology ; Disease Outbreaks ; Female ; Humans ; Infant ; Microcephaly/epidemiology ; Microcephaly/virology ; Pregnancy ; Public Health ; Zika Virus/metabolism ; Zika Virus/pathogenicity ; Zika Virus Infection/epidemiology ; Zika Virus Infection/physiopathology ; Zika Virus Infection/transmission
    Sprache Englisch
    Erscheinungsdatum 2020-03-03
    Erscheinungsland Netherlands
    Dokumenttyp Journal Article ; Review
    ZDB-ID 186544-4
    ISSN 1573-4978 ; 0301-4851
    ISSN (online) 1573-4978
    ISSN 0301-4851
    DOI 10.1007/s11033-020-05349-y
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  10. Artikel: A Polytherapy Strategy Using Vincristine and ALK Inhibitors to Sensitise EML4-ALK-Positive NSCLC.

    Sampson, Josephina / Ju, Hyun-Min / Song, Ji-Young / Fry, Andrew M / Bayliss, Richard / Choi, Jene

    Cancers

    2022  Band 14, Heft 3

    Abstract: The oncogenic fusion of EML4-ALK is present in about 4-6% of non-small cell lung cancer (NSCLC). A targeted approach with ALK tyrosine kinase inhibitors (TKIs) has been proven highly effective in ALK-positive NSCLC patients. However, despite the initial ... ...

    Abstract The oncogenic fusion of EML4-ALK is present in about 4-6% of non-small cell lung cancer (NSCLC). A targeted approach with ALK tyrosine kinase inhibitors (TKIs) has been proven highly effective in ALK-positive NSCLC patients. However, despite the initial responses, the outcome of the treatment is variable. Previous studies have shown that the differential response depends in part on the type of EML4-ALK variant. Here, we examined the combination of ALK inhibitors and microtubule poison, vincristine, in cells expressing EML4-ALK V1 and V3, the two most common variants in NSCLC. We showed that combination therapy of ALK-TKIs with vincristine had anti-proliferative effects and blocked RAS/MAPK, PI3K/AKT and JAK/STAT3 signalling pathways in EML4-ALK V1 but not V3 cells. Our results demonstrate that high levels of tubulin acetylation are associated with poor response to vincristine in EML4-ALK V3 cells. Additionally, we demonstrated differences in microtubule stability between the two EML4-ALK fusions. EML4-ALK V3 cells exhibited dynamic microtubules that confer poor response to vincristine compared to V1 cells. Hence, we suggested that the portion of EML4 in the fusion has an important role for the outcome of the combination treatment.
    Sprache Englisch
    Erscheinungsdatum 2022-02-02
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers14030779
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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