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  1. Article ; Online: Low Radiation Environment Switches the Overgrowth-Induced Cell Apoptosis Toward Autophagy

    Mariafausta Fischietti / Emiliano Fratini / Daniela Verzella / Davide Vecchiotti / Daria Capece / Barbara Di Francesco / Giuseppe Esposito / Marco Balata / Luca Ioannuci / Pamela Sykes / Luigi Satta / Francesca Zazzeroni / Alessandra Tessitore / Maria Antonella Tabocchini / Edoardo Alesse

    Frontiers in Public Health, Vol

    2021  Volume 8

    Abstract: Low radiation doses can affect and modulate cell responses to various stress stimuli, resulting in perturbations leading to resistance or sensitivity to damage. To explore possible mechanisms taking place at an environmental radiation exposure, we set-up ...

    Abstract Low radiation doses can affect and modulate cell responses to various stress stimuli, resulting in perturbations leading to resistance or sensitivity to damage. To explore possible mechanisms taking place at an environmental radiation exposure, we set-up twin biological models, one growing in a low radiation environment (LRE) laboratory at the Gran Sasso National Laboratory, and one growing in a reference radiation environment (RRE) laboratory at the Italian National Health Institute (Istituto Superiore di Sanità, ISS). Studies were performed on pKZ1 A11 mouse hybridoma cells, which are derived from the pKZ1 transgenic mouse model used to study the effects of low dose radiation, and focused on the analysis of cellular/molecular end-points, such as proliferation and expression of key proteins involved in stress response, apoptosis, and autophagy. Cells cultured up to 4 weeks in LRE showed no significant differences in proliferation rate compared to cells cultured in RRE. However, caspase-3 activation and PARP1 cleavage were observed in cells entering to an overgrowth state in RRE, indicating a triggering of apoptosis due to growth-stress conditions. Notably, in LRE conditions, cells responded to growth stress by switching toward autophagy. Interestingly, autophagic signaling induced by overgrowth in LRE correlated with activation of p53. Finally, the gamma component of environmental radiation did not significantly influence these biological responses since cells grown in LRE either in incubators with or without an iron shield did not modify their responses. Overall, in vitro data presented here suggest the hypothesis that environmental radiation contributes to the development and maintenance of balance and defense response in organisms.
    Keywords low radiation environment ; LRE ; apoptosis ; autophagy ; PARP1 ; p53 ; Public aspects of medicine ; RA1-1270
    Subject code 610
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Next-generation sequencing

    Filippo Del Vecchio / Valentina Mastroiaco / Antinisca Di Marco / Chiara Compagnoni / Daria Capece / Francesca Zazzeroni / Carlo Capalbo / Edoardo Alesse / Alessandra Tessitore

    Journal of Translational Medicine, Vol 15, Iss 1, Pp 1-

    recent applications to the analysis of colorectal cancer

    2017  Volume 19

    Abstract: Abstract Since the establishment of the Sanger sequencing method, scientists around the world focused their efforts to progress in the field to produce the utmost technology. The introduction of next-generation sequencing (NGS) represents a revolutionary ...

    Abstract Abstract Since the establishment of the Sanger sequencing method, scientists around the world focused their efforts to progress in the field to produce the utmost technology. The introduction of next-generation sequencing (NGS) represents a revolutionary step and promises to lead to massive improvements in our understanding on the role of nucleic acids functions. Cancer research began to use this innovative and highly performing method, and interesting results started to appear in colorectal cancer (CRC) analysis. Several studies produced high-quality data in terms of mutation discovery, especially about actionable or less frequently mutated genes, epigenetics, transcriptomics. Analysis of results is unveiling relevant perspectives aiding to evaluate the response to therapies. Novel evidences have been presented also in other directions such as gut microbiota or CRC circulating tumor cells. However, despite its unquestioned potential, NGS poses some issues calling for additional studies. This review intends to offer a view of the state of the art of NGS applications to CRC through examination of the most important technologies and discussion of recent published results.
    Keywords Next-generation sequencing ; Colorectal cancer ; Precision medicine ; Targeted therapy ; Medicine ; R
    Language English
    Publishing date 2017-12-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Unlocking the NF-κB Conundrum

    Federica Begalli / Jason Bennett / Daria Capece / Daniela Verzella / Daniel D’Andrea / Laura Tornatore / Guido Franzoso

    Biomedicines, Vol 5, Iss 3, p

    Embracing Complexity to Achieve Specificity

    2017  Volume 50

    Abstract: Transcription factors of the nuclear factor κB (NF-κB) family are central coordinating regulators of the host defence responses to stress, injury and infection. Aberrant NF-κB activation also contributes to the pathogenesis of some of the most common ... ...

    Abstract Transcription factors of the nuclear factor κB (NF-κB) family are central coordinating regulators of the host defence responses to stress, injury and infection. Aberrant NF-κB activation also contributes to the pathogenesis of some of the most common current threats to global human health, including chronic inflammatory diseases, autoimmune disorders, diabetes, vascular diseases and the majority of cancers. Accordingly, the NF-κB pathway is widely considered an attractive therapeutic target in a broad range of malignant and non-malignant diseases. Yet, despite the aggressive efforts by the pharmaceutical industry to develop a specific NF-κB inhibitor, none has been clinically approved, due to the dose-limiting toxicities associated with the global suppression of NF-κB. In this review, we summarise the main strategies historically adopted to therapeutically target the NF-κB pathway with an emphasis on oncology, and some of the emerging strategies and newer agents being developed to pharmacologically inhibit this pathway.
    Keywords nuclear factor κB ; NF-κB inhibitors ; cancer ; IκB kinase ; Gadd45β ; ubiquitin ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2017-08-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Targeting Costimulatory Molecules to Improve Antitumor Immunity

    Daria Capece / Daniela Verzella / Mariafausta Fischietti / Francesca Zazzeroni / Edoardo Alesse

    Journal of Biomedicine and Biotechnology, Vol

    2012  Volume 2012

    Abstract: The full activation of T cells necessitates the concomitant activation of two signals, the engagement of T-cell receptor by peptide/major histocompatibility complex II and an additional signal delivered by costimulatory molecules. The best characterized ... ...

    Abstract The full activation of T cells necessitates the concomitant activation of two signals, the engagement of T-cell receptor by peptide/major histocompatibility complex II and an additional signal delivered by costimulatory molecules. The best characterized costimulatory molecules belong to B7/CD28 and TNF/TNFR families and play crucial roles in the modulation of immune response and improvement of antitumor immunity. Unfortunately, tumors often generate an immunosuppressive microenvironment, where T-cell response is attenuated by the lack of costimulatory molecules on the surface of cancer cells. Thus, targeting costimulatory pathways represent an attractive therapeutic strategy to enhance the antitumor immunity in several human cancers. Here, latest therapeutic approaches targeting costimulatory molecules will be described.
    Keywords Biotechnology ; TP248.13-248.65 ; Medicine ; R
    Language English
    Publishing date 2012-01-01T00:00:00Z
    Publisher Hindawi Limited
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Serum Biomarkers Identification by Mass Spectrometry in High-Mortality Tumors

    Alessandra Tessitore / Agata Gaggiano / Germana Cicciarelli / Daniela Verzella / Daria Capece / Mariafausta Fischietti / Francesca Zazzeroni / Edoardo Alesse

    International Journal of Proteomics, Vol

    2013  Volume 2013

    Keywords Biochemistry ; QD415-436 ; Organic chemistry ; QD241-441 ; Chemistry ; QD1-999 ; Science ; Q ; DOAJ:Biochemistry ; DOAJ:Life Sciences ; DOAJ:Biology and Life Sciences
    Language English
    Publishing date 2013-01-01T00:00:00Z
    Publisher Hindawi Publishing Corporation
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: The Inflammatory Microenvironment in Hepatocellular Carcinoma

    Daria Capece / Mariafausta Fischietti / Daniela Verzella / Agata Gaggiano / Germana Cicciarelli / Alessandra Tessitore / Francesca Zazzeroni / Edoardo Alesse

    BioMed Research International, Vol

    A Pivotal Role for Tumor-Associated Macrophages

    2013  Volume 2013

    Abstract: Hepatocellular carcinoma (HCC) is one of the most common and aggressive human cancers worldwide. HCC is an example of inflammation-related cancer and represents a paradigm of the relation occurring between tumor microenvironment and tumor development. ... ...

    Abstract Hepatocellular carcinoma (HCC) is one of the most common and aggressive human cancers worldwide. HCC is an example of inflammation-related cancer and represents a paradigm of the relation occurring between tumor microenvironment and tumor development. Tumor-associated macrophages (TAMs) are a major component of leukocyte infiltrate of tumors and play a pivotal role in tumor progression of inflammation-related cancer, including HCC. Several studies indicate that, in the tumor microenvironment, TAMs acquire an M2-polarized phenotype and promote angiogenesis, metastasis, and suppression of adaptive immunity through the expression of cytokines, chemokines, growth factors, and matrix metalloproteases. Indeed, an established M2 macrophage population has been associated with poor prognosis in HCC. The molecular links that connect cancer cells and TAMs are not completely known, but recent studies have demonstrated that NF-κB, STAT-3, and HIF-1 signaling pathways play key roles in this crosstalk. In this paper, we discuss the current knowledge about the role of TAMs in HCC development, highlighting the role of TAM-derived cytokines, chemokines, and growth factors in the initiation and progression of liver cancer and outlining the signaling pathways involved in the interplay between cancer cells and TAMs.
    Keywords Medicine ; R
    Subject code 610
    Language English
    Publishing date 2013-01-01T00:00:00Z
    Publisher Hindawi Limited
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: KCTD11 Tumor Suppressor Gene Expression Is Reduced in Prostate Adenocarcinoma

    Francesca Zazzeroni / Daniela Nicosia / Alessandra Tessitore / Rita Gallo / Daniela Verzella / Mariafausta Fischietti / Davide Vecchiotti / Luca Ventura / Daria Capece / Alberto Gulino / Edoardo Alesse

    BioMed Research International, Vol

    2014  Volume 2014

    Abstract: Prostate cancer is the most common noncutaneous cancer among men in the United States. A genetic contribution to prostate cancer risk has been documented, but knowledge of the molecular mechanisms involved in prostate cancer initiation is still not well ... ...

    Abstract Prostate cancer is the most common noncutaneous cancer among men in the United States. A genetic contribution to prostate cancer risk has been documented, but knowledge of the molecular mechanisms involved in prostate cancer initiation is still not well understood. Loss of heterozygosity (LOH) of chromosomal regions is crucial in tumor progression. In human prostate cancer, several chromosomal regions demonstrating a high frequency of LOH have been previously identified. KCTD11 (REN) is a tumor suppressor gene mapping on human chromosome 17p13.2, whose expression is frequently lost in human medulloblastoma and in several other cancer types. KCTD11 acts as a negative regulator of the Hedgehog (Hh) signaling. Here, we demonstrated that KCTD11 LOH is a common genetic lesion in human prostate adenocarcinoma. Indeed, nuclear KCTD11 protein expression is strongly reduced in primary prostate cancer, and this event correlated with overexpression of proteins acting into the Hedgehog pathway. Low levels of KCTD11 mRNA have been also observed in prostatic cancer cells, and ectopic overexpression of KCTD11 led to growth arrest. Our study demonstrates and supports that KCTD11, as well as negatively regulated downstream effectors belonging to Hh signaling, plays a role in prostate cancer pathogenesis. This could be suitable to characterize new diagnostic and therapeutic markers.
    Keywords Medicine ; R
    Subject code 570
    Language English
    Publishing date 2014-01-01T00:00:00Z
    Publisher Hindawi Limited
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: A novel, non-canonical splice variant of the Ikaros gene is aberrantly expressed in B-cell lymphoproliferative disorders.

    Daria Capece / Francesca Zazzeroni / Maria Michela Mancarelli / Daniela Verzella / Mariafausta Fischietti / Ambra Di Tommaso / Rita Maccarone / Sara Plebani / Mauro Di Ianni / Alberto Gulino / Edoardo Alesse

    PLoS ONE, Vol 8, Iss 7, p e

    2013  Volume 68080

    Abstract: The Ikaros gene encodes a Krüppel-like zinc-finger transcription factor involved in hematopoiesis regulation. Ikaros has been established as one of the most clinically relevant tumor suppressors in several hematological malignancies. In fact, expression ... ...

    Abstract The Ikaros gene encodes a Krüppel-like zinc-finger transcription factor involved in hematopoiesis regulation. Ikaros has been established as one of the most clinically relevant tumor suppressors in several hematological malignancies. In fact, expression of dominant negative Ikaros isoforms is associated with adult B-cell acute lymphoblastic leukemia, myelodysplastic syndrome, acute myeloid leukemia and adult and juvenile chronic myeloid leukemia. Here, we report the isolation of a novel, non-canonical Ikaros splice variant, called Ikaros 11 (Ik11). Ik11 is structurally related to known dominant negative Ikaros isoforms, due to the lack of a functional DNA-binding domain. Interestingly, Ik11 is the first Ikaros splice variant missing the transcriptional activation domain. Indeed, we demonstrated that Ik11 works as a dominant negative protein, being able to dimerize with Ikaros DNA-binding isoforms and inhibit their functions, at least in part by retaining them in the cytoplasm. Notably, we demonstrated that Ik11 is the first dominant negative Ikaros isoform to be aberrantly expressed in B-cell lymphoproliferative disorders, such as chronic lymphocytic leukemia. Aberrant expression of Ik11 interferes with both proliferation and apoptotic pathways, providing a mechanism for Ik11 involvement in tumor pathogenesis. Thus, Ik11 could represent a novel marker for B-cell lymphoproliferative disorders.
    Keywords Medicine ; R ; Science ; Q
    Subject code 572
    Language English
    Publishing date 2013-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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