A5017409764- Liver physiology and pathology
- Cancer Cells and Metastasis
- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Cancer Research and Treatments
- Lung Cancer Research Studies
- PI3K/AKT/mTOR signaling in cancer
- Pancreatic and Hepatic Oncology Research
- Monoclonal and Polyclonal Antibodies Research
- Cancer, Hypoxia, and Metabolism
- FOXO transcription factor regulation
- Cancer Mechanisms and Therapy
- Lung Cancer Treatments and Mutations
- Microtubule and mitosis dynamics
- 3D Printing in Biomedical Research
- Immune Cell Function and Interaction
- Glycosylation and Glycoproteins Research
- Ferroptosis and cancer prognosis
- CAR-T cell therapy research
- Phagocytosis and Immune Regulation
- Histone Deacetylase Inhibitors Research
- Melanoma and MAPK Pathways
- Neuroethics, Human Enhancement, Biomedical Innovations
- Thyroid Cancer Diagnosis and Treatment
- Microfluidic and Bio-sensing Technologies
University of Palermo
2021-2025
Istituti di Ricovero e Cura a Carattere Scientifico
2016-2023
Candiolo Cancer Institute
2016-2023
Ospedale Misericordia - Grosseto
2020
University of Turin
2016-2019
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....
In light of the emerging breakthroughs in cancer biology, drug discovery, and personalized medicine, Tumor-on-Chip (ToC) platforms have become pivotal tools current biomedical research. This study introduced a novel rapid prototyping approach for fabrication ToC device using laser-patterned poly(methyl methacrylate) (PMMA) layers integrated with polylactic acid (PLA) electrospun scaffold, enabling dynamic delivery assessment therapeutic efficacy cells. Traditional screening methods, such as...
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...
Interferon-induced expression of programmed cell death ligands (PD-L1/PD-L2) may sustain tumour immune-evasion. Patients featuring MET amplification, a genetic lesion driving transformation, benefit from anti-MET treatment. We explored if MET-targeted therapy interferes with Interferon-γ modulation PD-L1/PD-L2 in MET-amplified tumours. and signalling pathways downstream or were analysed lines patient-derived organoids, basal condition, upon stimulation, after therapy. PD-L1 PD-L2 upregulated...
Abstract Objectives To explore the impact of sex and age on relationship between prodromal constipation disease phenotype in Parkinson’s at early stages. Methods A total 385 patients from PRIAMO study were classified according to presence followed for 24 months. Multivariable mixed-effect models applied. All analyses performed separately (64.1% men) median (different by sex: 67 years-old men 68 women). Results As sex, was associated with greater odds attention/memory complaints apathy...
Aberrant activation of the MET receptor in cancer is sustained by genetic alterations or, more frequently, transcriptional upregulations. A fraction MET-amplified or mutated tumors are sensible to targeting agents, but their responsiveness typically short-lasting, as secondary resistance eventually occurs. Since absence usually not a tumor driver, overexpressing not/poorly responsive targeted therapies. Consequently, vast majority exhibiting still represent an unmet medical need.Here we...
Pancreatic ductal adenocarcinoma is an aggressive tumor characterized by the presence of abundant stromal compartment contributing significantly to malignant phenotype. stellate cells are peculiar fibroblasts present in stroma and represent predominant source extracellular matrix proteins, pro-inflammatory cytokines, growth factors, including hepatocyte factor (HGF). Exploiting a co-culture system human pancreatic cancer cells, we demonstrated that fibroblast activation was reduced upon...
The tyrosine kinase receptor encoded by the MET oncogene is a major player in cancer. When responsible for onset and progression of transformed phenotype (MET-addicted cancers), an efficient block its oncogenic activation results potent tumor growth inhibition.Here we describe molecular engineered antibody (hOA-DN30) validate pharmacological activity MET-addicted cancer models vitro vivo. Pharmacokinetics safety profile non-human primates have also been assessed.hOA-DN30 efficiently impaired...
MET, a master gene sustaining "invasive growth," is relevant target for cancer precision therapy. In the vast majority of tumors, wild-type MET behaves as "stress-response" and relies on ligand (HGF) to sustain cell "scattering," invasive growth apoptosis protection (oncogene "expedience"). this context, concomitant targeting HGF could be crucial reach effective inhibition. To test hypothesis, we combined an anti-MET antibody (MvDN30) inducing "shedding" (i.e., removal from surface), with...
The kinase receptor encoded by the Met oncogene is a sensible target for cancer therapy. chimeric monovalent Fab fragment of DN30 monoclonal antibody (MvDN30) has an odd mechanism action, based on cell surface removal via activation specific plasma membrane proteases. However, short half‐life Fab, due to its low molecular weight, severe limitation deployment in This issue was addressed increasing weight above glomerular filtration threshold through duplication constant domains, tandem...
Abstract Background The receptor encoded by the MET oncogene and its ligand Hepatocyte Growth Factor (HGF) are at core of invasive-metastatic behavior. In a number instances genetic alterations result in ligand-independent onset malignancy (MET addiction ). More frequently, stimulation wild-type contributes to progression toward metastasis expedience Thus, while inhibitors alone effective first case, combination therapy with is required second condition. Methods this paper, we generated...
Despite advances in the curative approach, survival rate of advanced colorectal cancer (CRC) patients is still poor, which likely due to emergence cell clones resistant available therapeutic options. We have already shown that CD44v6-positive CRC stem cells (CR-CSCs) are refractory toward standard anti-tumor agents activation PI3K pathway together with high HER2 expression levels. Tumor microenvironmental cytokines confer resistance CR-CSCs against HER2/PI3K targeting by enhancing MAPK...
Background Diffuse large B-cell lymphoma (DLBCL) is a hematological malignancy representing one-third of non-Hodgkin’s cases. Notwithstanding immunotherapy in combination with chemotherapy (R-CHOP) an effective therapeutic approach for DLBCL, subset patients encounters treatment resistance, leading to low survival rates. Thus, there urgent need identify predictive biomarkers DLBCL including the elderly population, which represents fastest-growing segment population Western countries. Methods...
Cancer cell dissemination is sustained by cell-autonomous and non-cell-autonomous functions. To disentangle the role of HGF (Hepatocyte Growth Factor) MET ligand/receptor axis in this complex process, we genetically knocked out gene cancer cells which not oncogenic driver. In way, evaluated contribution HGF/MET to independently its direct activities tumor microenvironment. The lack expression MET-/- has been proved molecular characterization. From a functional point view, stimulation was...
The MET oncogene encodes a tyrosine kinase receptor involved in the control of complex network biological responses that include protection from apoptosis and stimulation cell growth during embryogenesis, tissue regeneration, cancer progression. We previously developed an antagonist antibody (DN30) inducing physical removal surface resulting suppression to MET. In its bivalent form, displayed residual agonist activity, due dimerization lingering receptors, partial activation downstream...
<p>PD-L1/2 and phospho-p38 MAPK expression in NSCLC cells. Tumor membrane of PD-L1 PD-L2 cell lines was intensely enhanced by treatment with Interferon γ (n=9, p=0.02, p<0.0001) (A). Western blot analysis phosphorylated (p) total p38 cells (H1975) or without anti-PD-1 and/or PD-L1s (B).</p>
Abstract Background: MET, a master gene sustaining ‘invasive growth', is relevant target for cancer precision therapy. In limited number of cases, MET genetic lesion drives the malignant phenotype in ligand-independent manner (oncogene ‘addiction'). vast majority tumors, however, wild-type behaves as ‘stress-response' and relies on ligand (HGF) to sustain cell ‘scattering', invasive growth apoptosis protection ‘expedience'). this context -i.e. ligand-dependent activation- concomitant...