A5040112748- Cancer Immunotherapy and Biomarkers
- Cytokine Signaling Pathways and Interactions
- Colorectal Cancer Treatments and Studies
- interferon and immune responses
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Immune Response and Inflammation
- CAR-T cell therapy research
- Epigenetics and DNA Methylation
- Cancer Mechanisms and Therapy
- Immune cells in cancer
- Protein Tyrosine Phosphatases
- Signaling Pathways in Disease
- PI3K/AKT/mTOR signaling in cancer
- Cancer Research and Treatments
- T-cell and B-cell Immunology
- Glioma Diagnosis and Treatment
- Cell Adhesion Molecules Research
- Digestive system and related health
- Chemokine receptors and signaling
- Peptidase Inhibition and Analysis
- HIV Research and Treatment
- Histone Deacetylase Inhibitors Research
- 3D Printing in Biomedical Research
- Galectins and Cancer Biology
Istituto Superiore di Sanità
2012-2025
Icahn School of Medicine at Mount Sinai
2003-2004
Montefiore Medical Center
2002
Albert Einstein College of Medicine
2002
Yeshiva University
2002
Sapienza University of Rome
1994-2001
The gastrointestinal tract is lined by a layer of mucus comprised highly glycosylated proteins called mucins. To evaluate the importance mucin in intestinal carcinogenesis, we constructed mice genetically deficient Muc2, most abundant secreted mucin. Muc2-/- displayed aberrant crypt morphology and altered cell maturation migration. Most notably, frequently developed adenomas small intestine that progressed to invasive adenocarcinoma, as well rectal tumors. Thus, Muc2 involved suppression...
Aberrant signal transduction contributes substantially to leukemogenesis. The Janus kinase 1 (JAK1) gene encodes a cytoplasmic tyrosine that noncovalently associates with variety of cytokine receptors and plays nonredundant role in lymphoid cell precursor proliferation, survival, differentiation. We report somatic mutations JAK1 occur individuals acute lymphoblastic leukemia (ALL). were more prevalent among adult subjects the T ALL, where they accounted for 18% cases, associated advanced age...
Noonan syndrome is a developmental disorder with dysmorphic facies, short stature, cardiac defects, and skeletal anomalies, which can be caused by missense PTPN11 mutations. encodes Src homology 2 domain-containing tyrosine phosphatase (SHP2 or SHP-2), protein that acts in signal transduction downstream to growth factor, hormone, cytokine receptors. We compared the functional effects of three syndrome–causative mutations on SHP2's activity, interaction binding partner, transduction. All SHP2...
Immunotherapy efficacy relies on the crosstalk within tumor microenvironment between cancer and dendritic cells (DCs) resulting in induction of a potent effective antitumor response. DCs have specific role recognizing cells, taking up antigens (Ags) then migrating to lymph nodes for Ag (cross)-presentation naïve T cells. Interferon-α-conditioned (IFN-DCs) exhibit marked phagocytic activity special ability inducing Ag-specific T-cell Here, we developed novel microfluidic platform recreating...
The action of activin-A on Sertoli and spermatogonial cell proliferation during early postnatal life was studied by using in vitro organ culture testis fragments from 9-day-old rats. Activin significantly stimulated 3H-thymidine incorporation into cultured for 3 days the presence FSH, whereas it had no effect absence hormone. This dose dependent range 10-200 ng/ml specifically inhibited activin-binding protein, follistatin. activin upon different testicular cells detail...
// Sara Santagata 1 , Maria Napolitano Crescenzo D'Alterio Sonia Desicato 2 Salvatore Di Maro 3 Luciana Marinelli Alessandra Fragale 4 Buoncervello Francesco Persico 5 Lucia Gabriele Ettore Novellino Nicola Longo Sandro Pignata Sisto Perdonà and Stefania Scala Functional Genomics, Istituto Nazionale per lo Studio e la Cura dei Tumori, Fondazione “G. Pascale”-IRCCS, 80131 Naples, Italy Uro-Gynecological Department, Department of Pharmacy, University Naples Federico II,...
Abstract Regulatory T (Treg) cells are critical in inducing and maintaining tolerance. Despite progress understanding the basis of immune tolerance, mechanisms molecules involved generation Treg remain poorly understood. IFN regulatory factor (IRF)-1 is a pleiotropic transcription implicated regulation various processes. In this study, we report that IRF-1 negatively regulates CD4+CD25+ cell development function by specifically repressing Foxp3 expression. IRF-1-deficient (IRF-1−/−) mice...
Estrogens, in particular 17β-estradiol (E2), have a strong influence on the immune system and also affect pathological conditions such as autoimmune diseases. The biological effects of E2 are mediated by two intracellular receptors, i.e., estrogen receptor (ER)α ERβ, which function ligand-activated nuclear transcription factors producing genomic effects. Immune cells express both ERα ERβ that play complex role modulating inflammation. Phytoestrogens display estrogen-like Among them,...
The transcription factor interferon regulatory factor-8 (IRF-8) is crucial for myeloid cell development and immune response also acts as a tumor suppressor gene. Here, we analyzed the role of IRF-8 in cross talk between melanoma cells tumor-infiltrating leukocytes. B16-F10 transplanted into IRF-8-deficient (IRF-8-/-) mice grow more rapidly, leading to higher numbers lung metastasis, with respect control animals. These events correlated reduced dendritic T infiltration, accumulation...
A full elucidation of events occurring inside the cancer microenvironment is fundamental for optimization more effective therapies. In present study, cross-talk between and immune cells was examined by employing mice deficient (KO) in interferon regulatory factor (IRF)-8, a transcription essential induction competent responses. The vivo results showed that IRF-8 KO were highly permissive to B16.F10 melanoma growth metastasis due failure their exert proper immunosurveillance. These found be...
Infantile fibrosarcomas (IFS) and congenital mesoblastic nephroma (CMN) are rare myofibroblastic tumors of infancy early childhood commonly harboring the ETV6::NTRK3 gene fusion. IFS/CMN considered as with an 'intermediate prognosis' they locally aggressive, but rarely metastasize, generally have a favorable outcome. A fraction IFS/CMN-related neoplasms negative for rearrangement characterized by other chimeric proteins promoting MAPK signaling upregulation. In large proportion these tumors,...
Abstract Dendritic cells (DCs) are key players in melanoma immune surveillance, presenting tumor antigens to CD8+ T that target cells. However, the interaction between DCs and microenvironment is complex, shaped by tissue structures like endothelial vessels dynamic biological, chemical, physical factors. The immunosuppressive (TME) often hinders DC migration their ability initiate an effective anti-tumor response. Combining romidepsin, epigenetic agent, with type I interferon (IFN), known...
Abstract Members of the IFN regulatory factors (IRFs) family are transcriptional regulators that play essential roles in homeostasis and function immune system. Recent studies indicate a direct involvement some members development different subsets dendritic cells (DC). Here, we report IRF-1 is potent modulator functional maturation DC. IRF-1-deficient mice (IRF-1−/−) exhibited predominance plasmacytoid DC selective reduction conventional DC, especially CD8α+ subset. IRF-1−/− splenic were...
The antitumor effectiveness of cyclophosphamide (CTX) and other chemotherapeutics was shown to rely not only on direct cytotoxicity but also immunogenic tumor cell death systemic immunomodulatory mechanisms, including regulatory T (Treg) depletion, Th1 polarization, type I interferon (IFN) proinflammatory cytokine production. IFN factor (IRF)-1 is a transcriptional regulator IFNs IFN-inducible genes, involved in the control Treg differentiation sterile inflammation. Aim this study explore...
Abstract Background Tregs trafficking is controlled by CXCR4. In Renal Cell Carcinoma (RCC), the effect of new CXCR4 antagonist, R54, was explored in peripheral blood (PB)-Tregs isolated from primary RCC patients. Methods PB-Tregs were 77 patients and 38 healthy donors (HDs). CFSE-T effector-Tregs suppression assay, IL-35, IFN-γ, IL-10, TGF-β1 secretion, Nrp-1+ frequency evaluated. characterised for CTLA-4, PD-1, CD40L, PTEN, CD25, TGF-β1, FOXP3, DNMT1 transcriptional profile. PTEN-pAKT...
// Maria Buoncervello 1 , Giulia Romagnoli 1, * Mariachiara Buccarelli Alessandra Fragale Elena Toschi Stefania Parlato Donatella Lucchetti 2 Daniele Macchia Massimo Spada Irene Canini Sanchez 3 Mario Falchi 4 Martina Musella Mauro Biffoni Filippo Belardelli Imerio Capone Alessandro Sgambato Lucia Ricci Vitiani Gabriele Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy Patologia Generale, Università Cattolica del Sacro Cuore,...
Colorectal cancer results from the progressive accumulation of genetic and epigenetic alterations. IFN signaling defects play an important role in carcinogenesis process, which inability transcription regulatory factors (IRF) to access sequences IFN-stimulated genes (ISG) tumors immune cells may be pivotal. We reported that low-dose combination two FDA-approved epidrugs, azacytidine (A) romidepsin (R), with IFNα2 (ARI) hampers aggressiveness both colorectal metastatic stem vivo triggers...
Abstract Despite extensive studies that unraveled ligands and signal transduction pathways triggered by TLRs, little is known about the regulation of TLR gene expression. TLR3 plays a crucial role in recognition viral pathogens induction immune responses myeloid DCs. IFN regulatory factor (IRF)-8, member IRF family, transcriptional regulator essential roles development function lineage, affecting different subsets In this study, we show IRF-8 negatively controls expression suppressing IRF-1–...
CS proteins have been involved in the repair of a wide variety DNA lesions. Here, we analyse role break by studying histone H2AX phosphorylation different cell cycle phases and comet assay CS-A CS-B primary transformed cells. Following methyl methane sulphate treatment significant accumulation unrepaired single strand breaks was detected cells as compared to normal cells, leading double S G2 phases. A delay DSBs were also observed following IR exposure. These data confirm CSB suppression...