A5017461647- Cancer, Lipids, and Metabolism
- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Retinoids in leukemia and cellular processes
- Peroxisome Proliferator-Activated Receptors
- Cancer Cells and Metastasis
- Immunotherapy and Immune Responses
- Metabolism, Diabetes, and Cancer
- Cancer, Hypoxia, and Metabolism
- Immune Cell Function and Interaction
- PARP inhibition in cancer therapy
- Single-cell and spatial transcriptomics
- Cancer Genomics and Diagnostics
- Chemokine receptors and signaling
- RNA modifications and cancer
- Cancer Research and Treatments
- MicroRNA in disease regulation
- Circular RNAs in diseases
- Lymphoma Diagnosis and Treatment
- Biochemical Analysis and Sensing Techniques
- Animal Genetics and Reproduction
- Chronic Lymphocytic Leukemia Research
- Public Health and Nutrition
- PI3K/AKT/mTOR signaling in cancer
- RNA Interference and Gene Delivery
European Institute of Oncology
2016-2025
Politecnico di Milano
2023-2025
Istituti di Ricovero e Cura a Carattere Scientifico
2023-2025
Ripamonti
2016-2025
Fondazione IRCCS Istituto Nazionale dei Tumori
2022
The biguanide metformin is used in type 2 diabetes management and has gained significant attention as a potential cancer preventive agent. Angioprevention represents mechanism of chemoprevention, yet conflicting data concerning the antiangiogenic action have emerged. Here, we clarify some contradictory effects on endothelial cells angiogenesis, using vitro vivo assays combined with transcriptomic protein array approaches. Metformin inhibits formation capillary-like networks by cells; this...
The human white adipose tissue (WAT) contains progenitors with cooperative roles in breast cancer (BC) angiogenesis, local and metastatic progression. biguanide Metformin (Met), commonly used for Type 2 diabetes, might have activity against BC was found to inhibit angiogenesis vivo . We studied Met another biguanide, phenformin (Phe), vitro models. In , biguanides activated AMPK, inhibited Complex 1 of the respiratory chain induced apoptosis WAT endothelial cells. coculture, production...
Anti-PD-1 and anti-PD-L1 checkpoint inhibitors (CIs) are clinically active in many types of cancer. However, only a minority patients achieve complete and/or long-lasting clinical response. We studied the effects different doses three widely used, orally chemotherapeutics (vinorelbine, cyclophosphamide 5-FU) over local metastatic tumour growth, landscape circulating tumour-infiltrating immune cells involved CI activity.Immunocompetent Balb/c mice were used to generate models breast cancer...
Obesity is associated with an increased frequency, morbidity, and mortality of several types neoplastic diseases, including postmenopausal breast cancer. We found that human adipose tissue contains two populations progenitors cooperative roles in CD45(-)CD34(+)CD31(+)CD13(-)CCRL2(+) endothelial cells can generate mature capillaries. Their cancer-promoting effect the was limited absence CD45(-)CD34(+)CD31(-)CD13(+)CD140b(+) mesenchymal progenitors/adipose stromal (ASC), which generated...
A cell population with progenitor-like phenotype (CD45-CD34+) resident in human white adipose tissue (WAT) is known to promote the progression of local and metastatic breast cancer angiogenesis. However, molecular mechanisms interaction have not been elucidated. In this study, we identified two proteins that were significantly upregulated WAT-derived progenitors after coculture cancer: granulocyte macrophage colony-stimulating factor (GM-CSF) matrix metallopeptidase 9 (MMP9). These released...
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic malignancy for which there still no effective therapy. In order to identify genetic alterations useful new treatment design, we used whole-exome sequencing analyze 14 BPDCN patients the patient-derived CAL-1 line. The functional enrichment analysis of mutational data reported epigenetic regulatory program be most significantly undermined (P
Monoclonal antibodies (mAbs) have significantly improved the treatment of certain cancers.However, in general mAbs alone limited clinical activity.One their main mechanisms action is to induce antibody-dependent cell-mediated cytotoxicity (ADCC), which mediated by natural killer (NK) cells.However, most cancer patients present severe immune dysfunctions affecting NK activity.This could be circumvented injection allogeneic, expanded, cells, safe.Nevertheless, despite strong cytolytic...
Genomic instability plays a pathological role in various malignancies, including acute myeloid leukemia (AML), and thus represents potential therapeutic target. Recent studies demonstrate that SIRT6, NAD+-dependent nuclear deacetylase, functions as genome-guardian by preserving DNA integrity different tumor cells. Here, we also CD34+ blasts from AML patients show ongoing damage SIRT6 overexpression. Indeed, identified poor-prognostic subset of patients, with widespread instability, which...
Tumor cell metabolism is altered during leukemogenesis. Cells performing oxidative phosphorylation (OXPHOS) generate reactive oxygen species (ROS) through mitochondrial activity. To limit the deleterious effects of excess ROS, certain gene promoters contain antioxidant response elements (ARE), e.g. genes NQO-1 and HO-1. ROS induces conformational changes in KEAP1 releases NRF2, which activates AREs. We show vitro vivo that OXPHOS induces, both primary leukemic cells lines, de novo expression...
Abstract Metformin can induce breast cancer (BC) cell apoptosis and reduce BC local metastatic growth in preclinical models. Since is frequently used along with Aspirin or beta-blockers, we investigated the effect of Metformin, beta-blocker Atenolol several In vitro , synergized inducing triple negative endocrine-sensitive cells activating AMPK white adipose tissue (WAT) progenitors known to cooperate progression. Both added inhibitory against complex I respiratory chain. both...
Abstract Checkpoint inhibitors (CI) instigate anticancer immunity in many neoplastic diseases, albeit only a fraction of patients. The clinical success cyclophosphamide (C)-based haploidentical stem-cell transplants indicates that this drug may re-orchestrate the immune system. Using models triple-negative breast cancer (TNBC) with different intratumoral contexture, we demonstrate combinatorial therapy intermittent C, CI, and vinorelbine activates antigen-presenting cells (APC), abrogates...
Leukemic cells proliferate faster than non-transformed counterparts. This requires them to change their metabolism adapt high growth. can stress and facilitate recognition by immune such as cytotoxic lymphocytes, which express the activating receptor Natural Killer G2-D (NKG2D). The tumor suppressor gene p53 regulates cell metabolism, but its role in expression of metabolism-induced ligands, subsequent is unknown. We show here that dichloroacetate (DCA), induces oxidative phosphorylation...
Abstract Solid tumor cells have an altered metabolism that can protect them from cytotoxic lymphocytes. The anti-diabetic drug metformin modifies cell and several clinical trials are testing its effectiveness for the treatment of solid cancers. use in hematologic cancers has received much less attention, although allogeneic lymphocytes very effective against these tumors. We show here induces expression Natural Killer G2-D (NKG2D) ligands (NKG2DL) intercellular adhesion molecule-1 (ICAM-1),...
// Valentina Salvestrini 1 , Stefania Orecchioni 2 Giovanna Talarico Francesca Reggiani Cristina Mazzetti 3 Francesco Bertolini Elisa Orioli 4 Elena Adinolfi Di Virgilio Annalisa Pezzi Michele Cavo Roberto M Lemoli 5, * Antonio Curti 1, Department of Experimental, Diagnostic and Specialty Medicine, University Bologna, Italy European Institute Oncology, Milan, Biomedical Neuromotor Sciences, Morphology, Surgery Experimental Ferrara, 5 Clinic Hematology, Internal Medicine (DiMI), Genoa, These...
Stromal cell-derived factor-1α (SDF-1α) drives endothelial colony-forming cell (ECFC) homing and incorporation within neovessels, thereby restoring tissue perfusion in ischemic tissues favoring tumor vascularization metastasis. SDF-1α stimulates ECFC migration by activating the Gi-protein-coupled receptor, CXCR4, then engaging phosphoinositide 3-kinase (PI3K)/AKT signaling pathway. Sporadic evidence showed that may also act through an increase intracellular Ca2+ concentration ([Ca2+]i) bone...
Abstract Non-small-cell lung carcinoma (NSCLC) is the most common cancer and one of pioneer tumors in which immunotherapy has radically changed patients’ outcomes. However, several issues are emerging their implementation required to optimize immunotherapy-based protocols. In this work, we investigate ability Bromodomain Extra-Terminal protein inhibitors (BETi) stimulate a proficient anti-tumor immune response toward NSCLC. By using vitro, ex-vivo, vivo models, demonstrate that these...
Oxidative phosphorylation (OXPHOS) generates ROS as a byproduct of mitochondrial complex I activity. ROS-detoxifying enzymes are made available through the activation their antioxidant response elements (ARE) in gene promoters. NRF2 binds to AREs and induces this anti-oxidant response. We show that cells from multiple origins performing OXPHOS induced expression its transcriptional The promoter contains MEF2 binding sites MAPK ERK5 MEF2-dependent expression. Blocking mouse model decreased...
Abstract Breast cancer (BC) constitutes a major health problem worldwide, making it the most common malignancy in women. Current treatment options for BC depend primarily on histological type, molecular markers, clinical aggressiveness and stage of disease. Immunotherapy, such as αPD-1, have shown combinatorial activity with chemotherapy triple negative breast (TNBC) delineating some therapeutic combinations more effective than others. However, clear overview main immune cell populations...
Abstract Immunity suffers a function deficit during aging, and the incidence of cancer is increased in elderly. However, most models employ young mice, which are poorly representative adult patients. We have previously reported that Triple-Therapy (TT), involving antigen-presenting-cell activation by vinorelbine generation TCF1 + -stem-cell-like T cells (scTs) cyclophosphamide significantly improved anti-PD-1 efficacy anti-PD1-resistant like Triple-Negative Breast Cancer (TNBC) Non-Hodgkin’s...
Overexpression of the antiapoptotic oncogene BCL-2 predicts poor prognosis in diffuse large B cell lymphoma (DLBCL) treated with anthracycline-based chemoimmunotherapy. Anthracyclines exert antitumor effects by multiple mechanisms including inhibition ribosome biogenesis (RiBi) through rRNA synthesis blockade. RiBi inhibitors induce p53 stabilization ribosomal proteins-MDM2-p53 pathway, stabilized levels depending on baseline rate. We found that BH3-mimetic venetoclax could not fully reverse...
Abstract Immunity declines with age, leading to functional deficits and an increased incidence of cancer in the elderly. Despite this, most models utilize young (6-8 week old) mice, which are not representative adult patients. Triple negative breast (TNBC) typically occurs around 30-50 years can be approximated 12 months mice. We previously demonstrated that a Triple-Therapy (TT) including APC activation via vinorelbine generation TCF1+ stem-cell-like T cells (scTs) by cyclophosphamide...
// Nerea Allende-Vega 1, * , Ewelina Krzywinska Stefania Orecchioni 2 Nuria Lopez-Royuela 1 Francesca Reggiani Giovanna Talarico Jean-François Rossi 3 Rodrigue Rossignol 4, 5 Yosr Hicheri Guillaume Cartron Francesco Bertolini Martin Villalba 6 INSERM U1183, Université de Montpellier UFR Médecine, Montpellier, France Laboratory of Hematology-Oncology, European Institute Oncology, Milan, Italy Département d'Hématologie Clinique, CHU 4 Laboratoire Maladies Rares: Génétique et Métabolisme...
Abstract Aberrant activation of the PI3K/Akt/mTOR pathway is a common feature acute myeloid leukemia (AML) patients contributing to chemoresistance, disease progression and unfavourable outcome. Therefore, inhibition this may represent potential therapeutic approach in AML. The aim study was evaluate pre-clinical activity NVP-BKM120 (BKM120), selective pan-class I PI3K inhibitor, on AML cell lines primary samples. Our results demonstrate that BKM120 abrogates signaling, promoting growth...