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  1. Article: Carbonic anhydrase IX subcellular localization in normoxic and hypoxic SH-SY5Y neuroblastoma cells is assisted by its C-terminal protein interaction domain.

    Succoio, Mariangela / Amiranda, Sara / Sasso, Emanuele / Marciano, Carmen / Finizio, Arianna / De Simone, Giuseppina / Garbi, Corrado / Zambrano, Nicola

    Heliyon

    2023  Volume 9, Issue 8, Page(s) e18885

    Abstract: The human carbonic anhydrase IX (CA IX) is a hypoxia-induced transmembrane protein belonging to the α-CA enzyme family. It has a crucial role in pH regulation in hypoxic cells and acts by buffering intracellular acidosis induced by hypoxia. Indeed, it is ...

    Abstract The human carbonic anhydrase IX (CA IX) is a hypoxia-induced transmembrane protein belonging to the α-CA enzyme family. It has a crucial role in pH regulation in hypoxic cells and acts by buffering intracellular acidosis induced by hypoxia. Indeed, it is frequently expressed in cancer cells, where it contributes to tumor progression. CA IX is also able to localize in the nucleus, where it contributes to 47S rRNA precursor genes transcription; however, the mechanisms assisting its nuclear translocation still remain unclear. The aim of our study was to deepen the understanding of the mechanisms involved in CA IX subcellular distribution. To this purpose, we implemented a site-directed mutagenesis approach targeting the C-terminal domain of CA IX and evaluated the subcellular distribution of the wild-type and mutant proteins in the SH-SY5Y cell line. The mutant proteins showed impaired binding ability and altered subcellular distribution in both normoxic and hypoxic conditions. Our data suggest that CA IX nuclear translocation depends on its transit through the secretory and the endocytic pathways.
    Language English
    Publishing date 2023-08-02
    Publishing country England
    Document type Journal Article
    ZDB-ID 2835763-2
    ISSN 2405-8440
    ISSN 2405-8440
    DOI 10.1016/j.heliyon.2023.e18885
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Reactivation of telomerase reverse transcriptase expression in cancer: the role of TERT promoter mutations.

    Tornesello, Maria Lina / Cerasuolo, Andrea / Starita, Noemy / Amiranda, Sara / Bonelli, Patrizia / Tuccillo, Franca Maria / Buonaguro, Franco M / Buonaguro, Luigi / Tornesello, Anna Lucia

    Frontiers in cell and developmental biology

    2023  Volume 11, Page(s) 1286683

    Abstract: Telomerase activity and telomere elongation are essential conditions for the unlimited proliferation of neoplastic cells. Point mutations in the core promoter region of the telomerase reverse transcriptase (TERT) gene have been found to occur at high ... ...

    Abstract Telomerase activity and telomere elongation are essential conditions for the unlimited proliferation of neoplastic cells. Point mutations in the core promoter region of the telomerase reverse transcriptase (TERT) gene have been found to occur at high frequencies in several tumour types and considered a primary cause of telomerase reactivation in cancer cells. These mutations promote TERT gene expression by multiple mechanisms, including the generation of novel binding sites for nuclear transcription factors, displacement of negative regulators from DNA G-quadruplexes, recruitment of epigenetic activators and disruption of long-range interactions between TERT locus and telomeres. Furthermore, TERT promoter mutations cooperate with TPP1 promoter nucleotide changes to lengthen telomeres and with mutated BRAF and FGFR3 oncoproteins to enhance oncogenic signalling in cancer cells. TERT promoter mutations have been recognized as an early marker of tumour development or a major indicator of poor outcome and reduced patients survival in several cancer types. In this review, we summarize recent findings on the role of TERT promoter mutations, telomerase expression and telomeres elongation in cancer development, their clinical significance and therapeutic opportunities.
    Language English
    Publishing date 2023-11-15
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2737824-X
    ISSN 2296-634X
    ISSN 2296-634X
    DOI 10.3389/fcell.2023.1286683
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: The common H232 STING allele shows impaired activities in DNA sensing, susceptibility to viral infection, and in monocyte cell function, while the HAQ variant possesses wild-type properties.

    Froechlich, Guendalina / Finizio, Arianna / Napolano, Alessandra / Amiranda, Sara / De Chiara, Arianna / Pagano, Pasqualina / Mallardo, Massimo / Leoni, Guido / Zambrano, Nicola / Sasso, Emanuele

    Scientific reports

    2023  Volume 13, Issue 1, Page(s) 19541

    Abstract: Different innate immune pathways converge to Stimulator of interferon genes (STING) and trigger type I interferon responses after recognition of abnormal nucleic acids in the cells. This non-redundant function renders STING a major player in ... ...

    Abstract Different innate immune pathways converge to Stimulator of interferon genes (STING) and trigger type I interferon responses after recognition of abnormal nucleic acids in the cells. This non-redundant function renders STING a major player in immunosurveillance, and an emerging target for cancer and infectious diseases therapeutics. Beyond somatic mutations that often occur in cancer, the human gene encoding STING protein, TMEM173 (STING1), holds great genetic heterogeneity; R232, HAQ (R71H-G230A-R293Q) and H232 are the most common alleles. Although some of these alleles are likely to be hypomorphic, their function is still debated, due to the available functional assessments, which have been performed in biased biological systems. Here, by using genetic background-matched models, we report on the functional evaluation of R232, HAQ and H232 variants on STING function, and on how these genotypes affect the susceptibility to clinically relevant viruses, thus supporting a potential contributing cause to differences in inter-individual responses to infections. Our findings also demonstrate a novel toll-like receptor-independent role of STING in modulating monocytic cell function and differentiation into macrophages. We further supported the interplay of STING1 variants and human biology by demonstrating how monocytes bearing the H232 allele were impaired in M1/M2 differentiation, interferon response and antigen presentation. Finally, we assessed the response to PD-1 inhibitor in a small cohort of melanoma patients stratified according to STING genotype. Given the contribution of the STING protein in sensing DNA viruses, bacterial pathogens and misplaced cancer DNA, these data may support the development of novel therapeutic options for infectious diseases and cancer.
    MeSH term(s) Humans ; Alleles ; Communicable Diseases/genetics ; DNA ; Immunity, Innate/genetics ; Interferon Type I/metabolism ; Monocytes/metabolism ; Neoplasms/genetics ; Virus Diseases/genetics
    Chemical Substances DNA (9007-49-2) ; Interferon Type I ; STING1 protein, human
    Language English
    Publishing date 2023-11-09
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-023-46830-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Thyroid Hormone Enhances Angiogenesis and the Warburg Effect in Squamous Cell Carcinomas.

    Miro, Caterina / Nappi, Annarita / Cicatiello, Annunziata Gaetana / Di Cicco, Emery / Sagliocchi, Serena / Murolo, Melania / Belli, Valentina / Troiani, Teresa / Albanese, Sandra / Amiranda, Sara / Zavacki, Ann Marie / Stornaiuolo, Mariano / Mancini, Marcello / Salvatore, Domenico / Dentice, Monica

    Cancers

    2021  Volume 13, Issue 11

    Abstract: Cancer angiogenesis is required to support energetic demand and metabolic stress, particularly during conditions of hypoxia. Coupled to neo-vasculogenesis, cancer cells rewire metabolic programs to sustain growth, survival and long-term maintenance. ... ...

    Abstract Cancer angiogenesis is required to support energetic demand and metabolic stress, particularly during conditions of hypoxia. Coupled to neo-vasculogenesis, cancer cells rewire metabolic programs to sustain growth, survival and long-term maintenance. Thyroid hormone (TH) signaling regulates growth and differentiation in a variety of cell types and tissues, thus modulating hyper proliferative processes such as cancer. Herein, we report that TH coordinates a global program of metabolic reprogramming and induces angiogenesis through up-regulation of the
    Language English
    Publishing date 2021-06-01
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers13112743
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Generation of a Retargeted Oncolytic

    Gentile, Chiara / Finizio, Arianna / Froechlich, Guendalina / D'Alise, Anna Morena / Cotugno, Gabriella / Amiranda, Sara / Nicosia, Alfredo / Scarselli, Elisa / Zambrano, Nicola / Sasso, Emanuele

    International journal of molecular sciences

    2021  Volume 22, Issue 24

    Abstract: Background: Oncolytic viruses are immunotherapeutic agents that can be engineered to encode payloads of interest within the tumor microenvironment to enhance therapeutic efficacy. Their therapeutic potential could be limited by many avenues for immune ... ...

    Abstract Background: Oncolytic viruses are immunotherapeutic agents that can be engineered to encode payloads of interest within the tumor microenvironment to enhance therapeutic efficacy. Their therapeutic potential could be limited by many avenues for immune evasion exerted by the tumor. One such is mediated by adenosine, which induces pleiotropic immunosuppression by inhibiting antitumor immune populations as well as activating tolerogenic stimuli. Adenosine is produced starting from the highly immunostimulatory ATP, which is progressively hydrolyzed to ADP and adenosine by CD39 and CD73. Cancer cells express high levels of CD39 and CD73 ectoenzymes, thus converting immunostimulatory purinergic signal of ATP into an immunosuppressive signal. For this reason, CD39, CD73 and adenosine receptors are currently investigated in clinical trials as targets for metabolic cancer immunotherapy. This is of particular relevance in the context of oncovirotherapy, as immunogenic cell death induced by oncolytic viruses causes the secretion of a high amount of ATP which is available to be quickly converted into adenosine.
    Methods: Here, we took advantage of adenosine deaminase enzyme that naturally converts adenosine into the corresponding inosine derivative, devoid of immunoregulatory function. We encoded ADA into an oncolytic targeted herpes virus redirected to human HER2. An engineered ADA with an ectopic signal peptide was also generated to improve enzyme secretion (ADA-SP).
    Results: Insertion of the expression cassette was not detrimental for viral yield and cancer cell cytotoxicity. The THV_ADA and THV_ADA-SP successfully mediated the secretion of functional ADA enzyme. In in vitro model of human monocytes THP1, this ability of THV_ADA and THV_ADA-SP resulted in the retrieval of eADO-exposed monocytes replication rate, suggesting the proficiency of the viruses in rescuing the immune function.
    Conclusions: Encoding ADA into oncolytic viruses revealed promising properties for preclinical exploitation.
    MeSH term(s) Adenosine/genetics ; Adenosine Deaminase/genetics ; Antigens, CD/metabolism ; Cell Line ; Herpesviridae/genetics ; Humans ; Immunotherapy/methods ; Neoplasms/genetics ; Neoplasms/virology ; Oncolytic Virotherapy/methods ; Oncolytic Viruses/genetics ; THP-1 Cells ; Tumor Microenvironment/genetics
    Chemical Substances Antigens, CD ; Adenosine Deaminase (EC 3.5.4.4) ; Adenosine (K72T3FS567)
    Language English
    Publishing date 2021-12-16
    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/ijms222413521
    Database MEDical Literature Analysis and Retrieval System OnLINE

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