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Search Results: 1 - 3 of 3 matches for " Mariafausta Fischietti "
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Targeting Costimulatory Molecules to Improve Antitumor Immunity
Daria Capece,Daniela Verzella,Mariafausta Fischietti,Francesca Zazzeroni,Edoardo Alesse
Journal of Biomedicine and Biotechnology , 2012, DOI: 10.1155/2012/926321
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.
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 , 2013, DOI: 10.1155/2013/125858
Abstract: Cancer affects millions of people worldwide. Tumor mortality is substantially due to diagnosis at stages that are too late for therapies to be effective. Advances in screening methods have improved the early diagnosis, prognosis, and survival for some cancers. Several validated biomarkers are currently used to diagnose and monitor the progression of cancer, but none of them shows adequate specificity, sensitivity, and predictive value for population screening. So, there is an urgent need to isolate novel sensitive, specific biomarkers to detect the disease early and improve prognosis, especially in high-mortality tumors. Proteomic techniques are powerful tools to help in diagnosis and monitoring of treatment and progression of the disease. During the last decade, mass spectrometry has assumed a key role in most of the proteomic analyses that are focused on identifying cancer biomarkers in human serum, making it possible to identify and characterize at the molecular level many proteins or peptides differentially expressed. In this paper we summarize the results of mass spectrometry serum profiling and biomarker identification in high mortality tumors, such as ovarian, liver, lung, and pancreatic cancer. 1. Introduction Cancer-related mortality is one of the leading causes of death worldwide. The most effective treatment to fight cancer is still early diagnosis. On the other hand, it is known that the correct classification of the tumor, coupled to a suitable therapy and to a stringent follow-up, helps to prevent and detect relapses. Cancer is a very heterogeneous disease, and, at the diagnostic level, is defined by many indexes such as histological grade, tumor stage, patient age, sex and, more importantly, genetic background and profiles. Histological evaluation of tumor specimens obtained from tissue biopsy is the gold standard of diagnosis, but often tumors with the same histopathological features respond differently to the same therapy. New generation diagnostic platforms, previously unavailable, have enabled to better characterize transcriptomic signatures that predict tumor behaviour, helping to define diagnosis, prognosis, and the most appropriate therapies [1–3]. Tumor biomarker discovery in biological fluids, such as serum, plasma, and urine, is one of the most challenging aspects of proteomic research [4]. Many researchers have attempted to identify biomarkers in serum that reflect a particular pathophysiological state. Since the expressed proteins, native, fragmented, or posttranslationally modified, quickly change in response to environmental
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 , 2013, DOI: 10.1371/journal.pone.0068080
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.
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