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  1. Article ; Online: Once upon a Testis: The Tale of Cyclic Nucleotide Phosphodiesterase in Testicular Cancers.

    Campolo, Federica / Assenza, Maria Rita / Venneri, Mary Anna / Barbagallo, Federica

    International journal of molecular sciences

    2023  Volume 24, Issue 8

    Abstract: Phosphodiesterases are key regulators that fine tune the intracellular levels of cyclic nucleotides, given their ability to hydrolyze cAMP and cGMP. They are critical regulators of cAMP/cGMP-mediated signaling pathways, modulating their downstream ... ...

    Abstract Phosphodiesterases are key regulators that fine tune the intracellular levels of cyclic nucleotides, given their ability to hydrolyze cAMP and cGMP. They are critical regulators of cAMP/cGMP-mediated signaling pathways, modulating their downstream biological effects such as gene expression, cell proliferation, cell-cycle regulation but also inflammation and metabolic function. Recently, mutations in PDE genes have been identified and linked to human genetic diseases and PDEs have been demonstrated to play a potential role in predisposition to several tumors, especially in cAMP-sensitive tissues. This review summarizes the current knowledge and most relevant findings regarding the expression and regulation of PDE families in the testis focusing on PDEs role in testicular cancer development.
    MeSH term(s) Male ; Humans ; Testicular Neoplasms/genetics ; Cyclic AMP/metabolism ; Phosphoric Diester Hydrolases/metabolism ; Cyclic GMP/metabolism
    Chemical Substances diethylstilbestrol monophosphate (47341-71-9) ; Cyclic AMP (E0399OZS9N) ; Phosphoric Diester Hydrolases (EC 3.1.4.-) ; Cyclic GMP (H2D2X058MU)
    Language English
    Publishing date 2023-04-20
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms24087617
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Cell Shortening and Calcium Homeostasis Analysis in Adult Cardiomyocytes via a New Software Tool.

    Fassina, Lorenzo / Assenza, Maria Rita / Miragoli, Michele / Isidori, Andrea M / Naro, Fabio / Barbagallo, Federica

    Biomedicines

    2022  Volume 10, Issue 3

    Abstract: Intracellular calcium ( ... ...

    Abstract Intracellular calcium (Ca
    Language English
    Publishing date 2022-03-10
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2720867-9
    ISSN 2227-9059
    ISSN 2227-9059
    DOI 10.3390/biomedicines10030640
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: p53 Activation Effect in the Balance of T Regulatory and Effector Cell Subsets in Patients With Thyroid Cancer and Autoimmunity.

    Arena, Andrea / Stigliano, Antonio / Belcastro, Eugenia / Giorda, Ezio / Rosado, Maria Manuela / Grossi, Armando / Assenza, Maria Rita / Moretti, Fabiola / Fierabracci, Alessandra

    Frontiers in immunology

    2021  Volume 12, Page(s) 728381

    Abstract: Carcinomas evade the host immune system by negatively modulating CD4+ and CD8+ T effector lymphocytes through forkhead box protein 3 (FOXP3) positive T regulatory cells' increased activity. Furthermore, interaction of the programmed cell death 1 (PD1) ... ...

    Abstract Carcinomas evade the host immune system by negatively modulating CD4+ and CD8+ T effector lymphocytes through forkhead box protein 3 (FOXP3) positive T regulatory cells' increased activity. Furthermore, interaction of the programmed cell death 1 (PD1) molecule and its ligand programmed cell death ligand 1 (PDL1) inhibits the antitumor activity of PD1+ T lymphocytes. Immunotherapy has become a powerful strategy for tailored cancer patients' treatment both in adult and pediatric patients aiming to generate potent antitumor responses. Nevertheless, immunotherapies can generate autoimmune responses. This study aimed to investigate the potential effect of the transformation-related protein 53 (p53) reactivation by a peptide-based inhibitor of the MDM2/MDM4 heterodimer (Pep3) on the immune response in a solid cancer,
    MeSH term(s) Adult ; Antineoplastic Agents/pharmacology ; Autoantibodies/blood ; Autoimmunity/drug effects ; Biomarkers/blood ; Case-Control Studies ; Cells, Cultured ; Female ; Humans ; Leukocytes, Mononuclear/drug effects ; Leukocytes, Mononuclear/immunology ; Leukocytes, Mononuclear/metabolism ; Lymphocytes, Tumor-Infiltrating/drug effects ; Lymphocytes, Tumor-Infiltrating/immunology ; Lymphocytes, Tumor-Infiltrating/metabolism ; Male ; Middle Aged ; Peptides/pharmacology ; Phenotype ; Programmed Cell Death 1 Receptor/metabolism ; T-Lymphocytes, Regulatory/drug effects ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/metabolism ; Thyroid Neoplasms/drug therapy ; Thyroid Neoplasms/immunology ; Thyroid Neoplasms/metabolism ; Tumor Suppressor Protein p53/metabolism
    Chemical Substances Antineoplastic Agents ; Autoantibodies ; Biomarkers ; PDCD1 protein, human ; Peptides ; Programmed Cell Death 1 Receptor ; TP53 protein, human ; Tumor Suppressor Protein p53 ; anti-thyroglobulin ; anti-thyroid autoantibodies
    Language English
    Publishing date 2021-08-30
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2021.728381
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Inhibition of the mTOR pathway and reprogramming of protein synthesis by MDM4 reduce ovarian cancer metastatic properties.

    Lucà, Rossella / Assenza, Maria Rita / Maiullari, Fabio / Pieroni, Luisa / Maiullari, Silvia / Federici, Giulia / Marini, Federica / Rizzi, Roberto / Urbani, Andrea / Soddu, Silvia / Moretti, Fabiola

    Cell death & disease

    2021  Volume 12, Issue 6, Page(s) 558

    Abstract: Epithelial ovarian cancer (EOC) is a highly heterogeneous disease with a high death rate mainly due to the metastatic spread. The expression of MDM4, a well-known p53-inhibitor, is positively associated with chemotherapy response and overall survival (OS) ...

    Abstract Epithelial ovarian cancer (EOC) is a highly heterogeneous disease with a high death rate mainly due to the metastatic spread. The expression of MDM4, a well-known p53-inhibitor, is positively associated with chemotherapy response and overall survival (OS) in EOC. However, the basis of this association remains elusive. We show that in vivo MDM4 reduces intraperitoneal dissemination of EOC cells, independently of p53 and an immune-competent background. By 2D and 3D assays, MDM4 impairs the early steps of the metastatic process. A 3D-bioprinting system, ad hoc developed by co-culturing EOC spheroids and endothelial cells, showed reduced dissemination and intravasation into vessel-like structures of MDM4-expressing cells. Consistent with these data, high MDM4 levels protect mice from ovarian cancer-related death and, importantly, correlate with increased 15 y OS probability in large data set analysis of 1656 patients. Proteomic analysis of EOC 3D-spheroids revealed decreased protein synthesis and mTOR signaling, upon MDM4 expression. Accordingly, MDM4 does not further inhibit cell migration when its activity towards mTOR is blocked by genetic or pharmacological approaches. Importantly, high levels of MDM4 reduced the efficacy of mTOR inhibitors in constraining cell migration. Overall, these data demonstrate that MDM4 impairs EOC metastatic process by inhibiting mTOR activity and suggest the usefulness of MDM4 assessment for the tailored application of mTOR-targeted therapy.
    MeSH term(s) Animals ; Cell Cycle Proteins/metabolism ; Female ; Humans ; Mice ; Neoplasm Metastasis ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/mortality ; Proteomics/methods ; Proto-Oncogene Proteins/metabolism ; Survival Analysis ; TOR Serine-Threonine Kinases/metabolism
    Chemical Substances Cell Cycle Proteins ; MDM4 protein, human ; Proto-Oncogene Proteins ; MTOR protein, human (EC 2.7.1.1) ; TOR Serine-Threonine Kinases (EC 2.7.1.1)
    Language English
    Publishing date 2021-05-29
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2541626-1
    ISSN 2041-4889 ; 2041-4889
    ISSN (online) 2041-4889
    ISSN 2041-4889
    DOI 10.1038/s41419-021-03828-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: PDE2A Is Indispensable for Mouse Liver Development and Hematopoiesis.

    Barbagallo, Federica / Rotilio, Valentina / Assenza, Maria Rita / Aguanno, Salvatore / Orsini, Tiziana / Putti, Sabrina / Isidori, Andrea M / Lenzi, Andrea / Naro, Fabio / De Angelis, Luciana / Pellegrini, Manuela

    International journal of molecular sciences

    2020  Volume 21, Issue 8

    Abstract: Phosphodiesterase 2A (PDE2A) is a cAMP-cGMP hydrolyzing enzyme essential for mouse development and ... ...

    Abstract Phosphodiesterase 2A (PDE2A) is a cAMP-cGMP hydrolyzing enzyme essential for mouse development and the
    MeSH term(s) Animals ; Apoptosis/genetics ; Biomarkers ; Cell Differentiation ; Cyclic Nucleotide Phosphodiesterases, Type 2/genetics ; Cyclic Nucleotide Phosphodiesterases, Type 2/metabolism ; Endothelial Cells/metabolism ; Endothelium/metabolism ; Genotype ; Hematopoiesis/genetics ; Immunohistochemistry ; Liver/embryology ; Liver/metabolism ; Mice ; Mice, Transgenic ; Mutation ; Organogenesis/genetics ; Stem Cells/cytology ; Stem Cells/metabolism ; Stromal Cells/metabolism
    Chemical Substances Biomarkers ; Cyclic Nucleotide Phosphodiesterases, Type 2 (EC 3.1.4.17) ; Pde2a protein, mouse (EC 3.1.4.17)
    Language English
    Publishing date 2020-04-21
    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/ijms21082902
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Critical role of phosphodiesterase 2A in mouse congenital heart defects.

    Assenza, Maria Rita / Barbagallo, Federica / Barrios, Florencia / Cornacchione, Marisa / Campolo, Federica / Vivarelli, Elisabetta / Gianfrilli, Daniele / Auletta, Luigi / Soricelli, Andrea / Isidori, Andrea M / Lenzi, Andrea / Pellegrini, Manuela / Naro, Fabio

    Cardiovascular research

    2018  Volume 114, Issue 6, Page(s) 830–845

    Abstract: Aims: Phosphodiesterase 2 A (Pde2A), a cAMP-hydrolysing enzyme, is essential for mouse development; however, the cause of Pde2A knockout embryonic lethality is unknown. To understand whether Pde2A plays a role in cardiac development, hearts of Pde2A ... ...

    Abstract Aims: Phosphodiesterase 2 A (Pde2A), a cAMP-hydrolysing enzyme, is essential for mouse development; however, the cause of Pde2A knockout embryonic lethality is unknown. To understand whether Pde2A plays a role in cardiac development, hearts of Pde2A deficient embryos were analysed at different stage of development.
    Methods and results: At the stage of four chambers, Pde2A deficient hearts were enlarged compared to the hearts of Pde2A heterozygous and wild-type. Pde2A knockout embryos revealed cardiac defects such as absence of atrial trabeculation, interventricular septum (IVS) defects, hypertrabeculation and thinning of the myocardial wall and in rare cases they had overriding aorta and valves defects. E14.5 Pde2A knockouts showed reduced cardiomyocyte proliferation and increased apoptosis in the IVS and increased proliferation in the ventricular trabeculae. Analyses of E9.5 Pde2A knockout embryos revealed defects in cardiac progenitor and neural crest markers, increase of Islet1 positive and AP2 positive apoptotic cells. The expression of early cTnI and late Mef2c cardiomyocyte differentiation markers was strongly reduced in Pde2A knockout hearts. The master transcription factors of cardiac development, Tbx, were down-regulated in E14.5 Pde2A knockout hearts. Absence of Pde2A caused an increase of intracellular cAMP level, followed by an up-regulation of the inducible cAMP early repressor, Icer in fetal hearts. In vitro experiments on wild-type fetal cardiomyocytes showed that Tbx gene expression is down-regulated by cAMP inducers. Furthermore, Pde2A inhibition in vivo recapitulated the heart defects observed in Pde2A knockout embryos, affecting cardiac progenitor cells. Interestingly, the expression of Pde2A itself was dramatically affected by Pde2A inhibition, suggesting a potential autoregulatory loop.
    Conclusions: We demonstrated for the first time a direct relationship between Pde2A impairment and the onset of mouse congenital heart defects, highlighting a novel role for cAMP in cardiac development regulation.
    MeSH term(s) Animals ; Apoptosis ; Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Cyclic AMP/metabolism ; Cyclic AMP Response Element Modulator/genetics ; Cyclic AMP Response Element Modulator/metabolism ; Cyclic Nucleotide Phosphodiesterases, Type 2/deficiency ; Cyclic Nucleotide Phosphodiesterases, Type 2/genetics ; Fetal Heart/abnormalities ; Fetal Heart/enzymology ; Gene Expression Regulation, Developmental ; Genetic Predisposition to Disease ; Gestational Age ; Heart Defects, Congenital/enzymology ; Heart Defects, Congenital/genetics ; Heart Defects, Congenital/pathology ; LIM-Homeodomain Proteins/genetics ; LIM-Homeodomain Proteins/metabolism ; MEF2 Transcription Factors/genetics ; MEF2 Transcription Factors/metabolism ; Mice, Inbred C57BL ; Mice, Knockout ; Morphogenesis ; Myocytes, Cardiac/enzymology ; Myocytes, Cardiac/pathology ; Phenotype ; Signal Transduction ; T-Box Domain Proteins/genetics ; T-Box Domain Proteins/metabolism ; Transcription Factor AP-2/genetics ; Transcription Factor AP-2/metabolism ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Troponin I/genetics ; Troponin I/metabolism
    Chemical Substances Crem protein, mouse ; LIM-Homeodomain Proteins ; MEF2 Transcription Factors ; Mef2c protein, mouse ; T-Box Domain Proteins ; Transcription Factor AP-2 ; Transcription Factors ; Troponin I ; insulin gene enhancer binding protein Isl-1 ; Cyclic AMP Response Element Modulator (135844-64-3) ; Cyclic AMP (E0399OZS9N) ; Cyclic Nucleotide Phosphodiesterases, Type 2 (EC 3.1.4.17) ; Pde2a protein, mouse (EC 3.1.4.17)
    Language English
    Publishing date 2018-02-05
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80340-6
    ISSN 1755-3245 ; 0008-6363
    ISSN (online) 1755-3245
    ISSN 0008-6363
    DOI 10.1093/cvr/cvy030
    Database MEDical Literature Analysis and Retrieval System OnLINE

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