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  1. Article: HER2 and PD-L1 Expression in Gastric and Gastroesophageal Junction Cancer: Insights for Combinatorial Targeting Approaches.

    Freitas, Marta Baptista / Gullo, Irene / Leitão, Dina / Águas, Lúcia / Oliveira, Carla / Polónia, António / Gomes, Joana / Carneiro, Fátima / Reis, Celso Albuquerque / Duarte, Henrique Oliveira

    Cancers

    2024  Volume 16, Issue 6

    Abstract: Gastric and gastroesophageal junction adenocarcinomas (GA/GEJA) are associated with a poor prognosis, primarily due to late disease diagnosis. Human Epidermal Growth Factor Receptor 2 (HER2) overexpression and programmed death-ligand 1 (PD-L1) expression ...

    Abstract Gastric and gastroesophageal junction adenocarcinomas (GA/GEJA) are associated with a poor prognosis, primarily due to late disease diagnosis. Human Epidermal Growth Factor Receptor 2 (HER2) overexpression and programmed death-ligand 1 (PD-L1) expression are important biomarkers for treatment selection in locally advanced unresectable and metastatic GA/GEJA, and there is increasing interest in their role in earlier stages of disease. In this study, we aimed to evaluate HER2 and PD-L1 expression in a curative-intent GA/GEJA cohort to describe their expression patterns and analyze the association between HER2 expression and clinicopathological features. HER2 expression was evaluated in surgical and endoscopic submucosal dissection tumor samples, and PD-L1 was evaluated in HER2-positive cases. The clinical cohort included 107 patients, with 8.4% testing positive for HER2 (seven of whom also exhibited a PD-L1 combined positive score of ≥1. HER2 status was not significantly associated with survival outcomes. A pathologist-guided, region-specific analysis revealed that PD-L1 expression rarely overlaps with HER2-positive tumor areas. While the therapeutic implications of these observations remain unknown, these findings suggest that combination strategies targeting HER2 and PD-L1 might be directed toward distinct tumor subclones. The herein disclosed region-specific biomarker expression patterns may have important therapeutic and prognostic impacts, warranting further evaluation.
    Language English
    Publishing date 2024-03-20
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers16061227
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Candida albicans chitinase 3 with potential as a vaccine antigen: production, purification, and characterisation.

    Costa-Barbosa, Augusto / Ferreira, Diogo / Pacheco, Maria Inês / Casal, Margarida / Duarte, Henrique Oliveira / Gomes, Catarina / Barbosa, Ana Margarida / Torrado, Egídio / Sampaio, Paula / Collins, Tony

    Biotechnology journal

    2023  Volume 19, Issue 1, Page(s) e2300219

    Abstract: Chitinases are widely studied enzymes that have already found widespread application. Their continued development and valorisation will be driven by the identification of new and improved variants and/or novel applications bringing benefits to industry ... ...

    Abstract Chitinases are widely studied enzymes that have already found widespread application. Their continued development and valorisation will be driven by the identification of new and improved variants and/or novel applications bringing benefits to industry and society. We previously identified a novel application for chitinases wherein the Candida albicans cell wall surface chitinase 3 (Cht3) was shown to have potential in vaccine applications as a subunit antigen against fungal infections. In the present study, this enzyme was investigated further, developing production and purification protocols, enriching our understanding of its properties, and advancing its application potential. Cht3 was heterologously expressed in Pichia pastoris and a 4-step purification protocol developed and optimised: this involves activated carbon treatment, hydrophobic interaction chromatography, ammonium sulphate precipitation, and gel filtration chromatography. The recombinant enzyme was shown to be mainly O-glycosylated and to retain the epitopes of the native protein. Functional studies showed it to be highly specific, displaying activity on chitin, chitosan, and chito-oligosaccharides larger than chitotriose only. Furthermore, it was shown to be a stable enzyme, exhibiting activity, and stability over broad pH and temperature ranges. This study represents an important step forward in our understanding of Cht3 and contributes to its development for application.
    MeSH term(s) Candida albicans/genetics ; Candida albicans/metabolism ; Chitinases/genetics ; Chitinases/chemistry ; Proteins ; Chitin/chemistry ; Chitin/metabolism ; Chitosan ; Hydrogen-Ion Concentration
    Chemical Substances Chitinases (EC 3.2.1.14) ; Proteins ; Chitin (1398-61-4) ; Chitosan (9012-76-4)
    Language English
    Publishing date 2023-10-30
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2221885-3
    ISSN 1860-7314 ; 1860-6768
    ISSN (online) 1860-7314
    ISSN 1860-6768
    DOI 10.1002/biot.202300219
    Database MEDical Literature Analysis and Retrieval System OnLINE

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