A5006462998- Neuroblastoma Research and Treatments
- Cancer Cells and Metastasis
- Cancer, Hypoxia, and Metabolism
- Protein Degradation and Inhibitors
- Ubiquitin and proteasome pathways
- Epigenetics and DNA Methylation
- Microtubule and mitosis dynamics
- Cancer therapeutics and mechanisms
- Cytokine Signaling Pathways and Interactions
- Histone Deacetylase Inhibitors Research
- FOXO transcription factor regulation
- Cancer-related molecular mechanisms research
- PI3K/AKT/mTOR signaling in cancer
- Cell death mechanisms and regulation
- interferon and immune responses
- DNA Repair Mechanisms
- Erythrocyte Function and Pathophysiology
- Mesenchymal stem cell research
- Colorectal Cancer Treatments and Studies
- Genetics and Neurodevelopmental Disorders
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Signaling Pathways in Disease
- Genomics and Chromatin Dynamics
- Neuroethics, Human Enhancement, Biomedical Innovations
University of Palermo
2018-2025
Sapienza University of Rome
2008-2025
Center for Cancer Research
2016-2024
National Cancer Institute
2015-2024
San Gallicano Hospital
2023
Istituti di Ricovero e Cura a Carattere Scientifico
2023
National Institutes of Health
2017
Institute of Molecular and Cell Biology
2017
Alder Hey Children's NHS Foundation Trust
2010
Bambino Gesù Children's Hospital
2010
Pharmacologically difficult targets, such as MYC transcription factors, represent a major challenge in cancer therapy. For the childhood neuroblastoma, amplification of oncogene MYCN is associated with high-risk disease and poor prognosis. Here, we deployed genome-scale CRISPR-Cas9 screening MYCN-amplified neuroblastoma found preferential dependency on genes encoding polycomb repressive complex 2 (PRC2) components EZH2, EED, SUZ12. Genetic pharmacological suppression EZH2 inhibited growth...
Cancer stem cells are responsible for tumour spreading and relapse. Human epidermal growth factor receptor 2 (HER2) expression is a negative prognostic in colorectal cancer (CRC) potential target tumours carrying the gene amplification. Our aim was to define of HER2 (CR-CSCs) its possible role as therapeutic CRC resistant anti- (EGFR) therapy.A collection primary sphere cell cultures obtained from 60 specimens used generate CR-CSC mouse avatars preclinically validate options. We also made...
Abstract Obesity is a strong risk factor for cancer progression, posing obesity-related as one of the leading causes death. Nevertheless, molecular mechanisms that endow cells with metastatic properties in patients affected by obesity remain unexplored. Here, we show IL-6 and HGF, secreted tumor neighboring visceral adipose stromal (V-ASCs), expand colorectal (CR) cell compartment (CD44v6 + ), which turn secretes neurotrophins such NGF NT-3, recruits stem within mass. Visceral...
It has been proposed that mesenchymal stromal cells (MSCs) promote tumor progression by interacting with and other stroma in the complex network of microenvironment. We characterized MSCs isolated expanded from tissues pediatric patients diagnosed neuroblastomas (NB-MSCs) to define interactions microenvironment.Specimens were obtained 7 neuroblastoma (NB). Morphology, immunophenotype, differentiation capacity, proliferative growth, expression stemness neural markers evaluated. Moreover,...
Abstract Thyroid carcinoma (TC) is the most common malignancy of endocrine organs. The cell subpopulation in lineage hierarchy that serves as origin for different TC histotypes unknown. Human embryonic stem cells (hESCs) with appropriate vitro stimulation undergo sequential differentiation into thyroid progenitor (TPCs-day 22), which maturate thyrocytes (day 30). Here, we create follicular cell-derived TCs all based on specific genomic alterations delivered by CRISPR-Cas9 hESC-derived TPCs....
Abstract Purpose: Neuroblastoma is a pediatric tumor of peripheral sympathoadrenal neuroblasts. The long-term event-free survival children with high-risk neuroblastoma still poor despite the improvements current multimodality treatment protocols. Activated JAK/STAT3 pathway plays an important role in many human cancers, suggesting that targeting STAT3 promising strategy for treating neuroblastoma. Experimental Design: To evaluate biologic consequences specific neuroblastoma, we assessed...
Limited therapeutic options are available for advanced colorectal cancer (CRC). Herein, we report that exposure to a neo-synthetic bis(indolyl)thiazole alkaloid analog, nortopsentin 234 (NORA234), leads an initial reduction of proliferative and clonogenic potential CRC sphere cells (CR-CSphCs), followed by adaptive response selecting the CR-CSphC-resistant compartment. Cells spared treatment with NORA234 express high levels CD44v6, associated constitutive activation Wnt pathway. In...
Colorectal cancer (CRC) mortality is mainly caused by patient refractoriness to common anti-cancer therapies and consequent metastasis formation. Besides, the notorious toxic side effects of chemotherapy are a concurrent obstacle be tackled. Thus, new treatment approaches needed effectively improve outcomes. Compelling evidence demonstrated that stem cells (CSCs) responsible for failure relapse. New natural showed capabilities selectively target CSC subpopulation rendering them targetable...
In many tumors, the tumor suppressor TP53 is not mutated, but functionally inactivated. However, mechanisms underlying p53 functional inactivation remain poorly understood. SETD8 sole enzyme known to mono-methylate on lysine 382 (p53K382me1), resulting in inhibition of its pro-apoptotic and growth-arresting functions. We analyzed p53K382me1 expression clinical colorectal cancer (CRC) inflammatory bowel disease (IBD) samples. Histopathological examinations, RNA sequencing, ChIP assay...
The MRE11/RAD50/NBS1 (MRN) complex is a major sensor of DNA double strand breaks, whose role in controlling faithful replication and preventing stress also emerging. Inactivation the MRN invariably leads to developmental and/or degenerative neuronal defects, pathogenesis which still remains poorly understood. In particular, NBS1 gene mutations are associated with microcephaly strongly impaired cerebellar development, both humans mouse model. These phenotypes strikingly overlap those induced...
Breast cancer (BC) is the second cause of cancer-related deceases in worldwide female population. Despite successful treatment advances, 25% BC develops resistance to current therapeutic regimens, thereby remaining a major hurdle for patient management. Current therapies, targeting molecular events underpinning adaptive resistance, still require effort improve treatment. Using sphere cells (BCSphCs) as model, here we showed that stem-like express high levels Myc, which requires presence...
MYCN amplification occurs in approximately 20% of human neuroblastomas and is associated with early tumor progression poor outcome, despite intensive multimodal treatment. However, overexpression also sensitizes neuroblastoma cells to apoptosis. Thus, uncovering the molecular mechanisms linking apoptosis might contribute designing more efficient therapies for MYCN-amplified tumors. Here we show that MYCN-dependent sensitization requires activation p53 its phosphorylation at serine 46. The...
Abstract Despite intense research and clinical efforts, patients affected by advanced colorectal cancer (CRC) have still a poor prognosis. The discovery of (CR) stem cell (CSC) as the compartment responsible for tumor initiation propagation may provide new opportunities development therapeutic strategies. Given reduced sensitivity CR-CSCs to chemotherapy ability bone morphogenetic proteins (BMP) promote colonic differentiation, we aimed investigate whether an enhanced variant BMP7 (BMP7v)...
MYCN amplification occurs in about 20-25% of human neuroblastomas and characterizes the majority high-risk cases, which display less than 50% prolonged survival rate despite intense multimodal treatment. Somehow paradoxically, also sensitizes neuroblastoma cells to apoptosis, understanding molecular mechanisms might be relevant for therapy amplified neuroblastoma. We recently reported that apoptosis-sensitive phenotype induced by is linked stabilization p53 its proapoptotic kinase HIPK2. In...
Abstract Reactivation of the HMGA1 protoncogene is very frequent in human cancer, but still little known on molecular mechanisms leading to this event. Prompted by finding putative E2F binding sites promoter and deregulation RB/E2F1 pathway carcinogenesis, we investigated whether E2F1 might contribute regulation gene expression. Here report that induces interacting with a 193 bp region containing an site surrounded three Sp1 sites. Both gain loss function experiments indicate functionally...
The p53 oncosuppressor is very seldom mutated in neuroblastoma, but several mechanisms cooperate to its functional inactivation this tumor. Increased MDM2 levels, due genetic amplification or constitutive inhibition of p14( ARF), significantly contribute event highlighting reactivation as an attractive perspective for neuroblastoma treatment. In addition role tumorigenesis, MYCN sensitizes untransformed and cancer cells apoptosis. This associated a fine modulation the MDM2-p53 pathway....