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  1. Article ; Online: Growth hormone-releasing hormone antagonist MIA-602 inhibits inflammation induced by SARS-CoV-2 spike protein and bacterial lipopolysaccharide synergism in macrophages and human peripheral blood mononuclear cells.

    Granato, Giuseppina / Gesmundo, Iacopo / Pedrolli, Francesca / Kasarla, Ramesh / Begani, Laura / Banfi, Dana / Bruno, Stefania / Lopatina, Tatiana / Brizzi, Maria Felice / Cai, Renzhi / Sha, Wei / Ghigo, Ezio / Schally, Andrew V / Granata, Riccarda

    Frontiers in immunology

    2023  Volume 14, Page(s) 1231363

    Abstract: COVID-19 is characterized by an excessive inflammatory response and macrophage hyperactivation, leading, in severe cases, to alveolar epithelial injury and acute respiratory distress syndrome. Recent studies have reported that SARS-CoV-2 spike (S) ... ...

    Abstract COVID-19 is characterized by an excessive inflammatory response and macrophage hyperactivation, leading, in severe cases, to alveolar epithelial injury and acute respiratory distress syndrome. Recent studies have reported that SARS-CoV-2 spike (S) protein interacts with bacterial lipopolysaccharide (LPS) to boost inflammatory responses
    MeSH term(s) Humans ; COVID-19 ; Endothelial Cells ; Growth Hormone-Releasing Hormone/antagonists & inhibitors ; Inflammation/drug therapy ; Leukocytes, Mononuclear ; Lipopolysaccharides ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus ; Tumor Necrosis Factor-alpha
    Chemical Substances GHRH(1-29)NH2, (PhAc-Ada)(0)-Tyr(1), Arg(2), Fpa(5,6), Ala(8), Har(9), Tyr(Me)(10), His(11), Orn(12,) Abu(15), His(20), Orn(21), Nle(27), Arg(28), Har(29)- ; Growth Hormone-Releasing Hormone (9034-39-3) ; Lipopolysaccharides ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; Tumor Necrosis Factor-alpha
    Language English
    Publishing date 2023-08-15
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2023.1231363
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Antagonist of Growth Hormone-Releasing Hormone Potentiates the Antitumor Effect of Pemetrexed and Cisplatin in Pleural Mesothelioma.

    Gesmundo, Iacopo / Pedrolli, Francesca / Vitale, Nicoletta / Bertoldo, Alessia / Orlando, Giulia / Banfi, Dana / Granato, Giuseppina / Kasarla, Ramesh / Balzola, Federico / Deaglio, Silvia / Cai, Renzhi / Sha, Wei / Papotti, Mauro / Ghigo, Ezio / Schally, Andrew V / Granata, Riccarda

    International journal of molecular sciences

    2022  Volume 23, Issue 19

    Abstract: Pleural mesothelioma (PM) is an aggressive cancer with poor prognosis and no effective therapies, mainly caused by exposure to asbestos. Antagonists of growth hormone-releasing hormone (GHRH) display strong antitumor effects in many experimental cancers, ...

    Abstract Pleural mesothelioma (PM) is an aggressive cancer with poor prognosis and no effective therapies, mainly caused by exposure to asbestos. Antagonists of growth hormone-releasing hormone (GHRH) display strong antitumor effects in many experimental cancers, including lung cancer and mesothelioma. Here, we aimed to determine whether GHRH antagonist MIA-690 potentiates the antitumor effect of cisplatin and pemetrexed in PM. In vitro, MIA-690, in combination with cisplatin and pemetrexed, synergistically reduced cell viability, restrained cell proliferation and enhanced apoptosis, compared with drugs alone. In vivo, the same combination resulted in a strong growth inhibition of MSTO-211H xenografts, decreased tumor cell proliferation and increased apoptosis. Mechanistically, MIA-690, particularly with chemotherapeutic drugs, inhibited proliferative and oncogenic pathways, such as MAPK ERK1/2 and cMyc, and downregulated cyclin D1 and B1 mRNAs. Inflammatory pathways such as NF-kB and STAT3 were also reduced, as well as oxidative, angiogenic and tumorigenic markers (iNOS, COX-2, MMP2, MMP9 and HMGB1) and growth factors (VEGF and IGF-1). Overall, these findings strongly suggest that GHRH antagonists of MIA class, such as MIA-690, could increase the efficacy of standard therapy in PM.
    MeSH term(s) Cell Line, Tumor ; Cisplatin/pharmacology ; Cisplatin/therapeutic use ; Cyclin D1 ; Cyclooxygenase 2 ; Growth Hormone-Releasing Hormone ; HMGB1 Protein ; Humans ; Insulin-Like Growth Factor I/therapeutic use ; Matrix Metalloproteinase 2 ; Matrix Metalloproteinase 9/genetics ; Mesothelioma/drug therapy ; Mesothelioma/pathology ; Mesothelioma, Malignant ; NF-kappa B/metabolism ; Pemetrexed/pharmacology ; Pemetrexed/therapeutic use ; Pleural Neoplasms/drug therapy ; Pleural Neoplasms/pathology ; Vascular Endothelial Growth Factor A/metabolism
    Chemical Substances HMGB1 Protein ; NF-kappa B ; Vascular Endothelial Growth Factor A ; Pemetrexed (04Q9AIZ7NO) ; Cyclin D1 (136601-57-5) ; Insulin-Like Growth Factor I (67763-96-6) ; Growth Hormone-Releasing Hormone (9034-39-3) ; Cyclooxygenase 2 (EC 1.14.99.1) ; Matrix Metalloproteinase 2 (EC 3.4.24.24) ; Matrix Metalloproteinase 9 (EC 3.4.24.35) ; Cisplatin (Q20Q21Q62J)
    Language English
    Publishing date 2022-09-24
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms231911248
    Database MEDical Literature Analysis and Retrieval System OnLINE

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