A5060112940- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Chronic Lymphocytic Leukemia Research
- Chronic Myeloid Leukemia Treatments
- Immune Response and Inflammation
- S100 Proteins and Annexins
- Cell Adhesion Molecules Research
- Blood disorders and treatments
- Acute Myeloid Leukemia Research
- PARP inhibition in cancer therapy
- Hematopoietic Stem Cell Transplantation
- HER2/EGFR in Cancer Research
- Histone Deacetylase Inhibitors Research
- Biochemical and Molecular Research
- Ubiquitin and proteasome pathways
- Cancer Treatment and Pharmacology
- Cancer Genomics and Diagnostics
- Immunotherapy and Immune Responses
- Neutropenia and Cancer Infections
- Peptidase Inhibition and Analysis
- Calcium signaling and nucleotide metabolism
- Sirtuins and Resveratrol in Medicine
- Lymphoma Diagnosis and Treatment
- Protein Degradation and Inhibitors
- Computational Drug Discovery Methods
- RNA Interference and Gene Delivery
University of Genoa
2009-2018
Istituti di Ricovero e Cura a Carattere Scientifico
2012-2016
Ospedale Policlinico San Martino
2002-2016
Dana-Farber Cancer Institute
2012
Martin University
2012
Merrimack Pharmaceuticals (United States)
2004
University of Tübingen
2004
Massachusetts Institute of Technology
2004
Center for Cancer Research
2004
Harvard University Press
1992
Cytokine secretion by cancer cells contributes to cancer-induced symptoms and angiogenesis. Studies show that the sirtuin SIRT6 promotes inflammation enhancing TNF expression. Here, we aimed determine whether is involved in conferring an inflammatory phenotype define mechanisms linking inflammation. We enhances expression of pro-inflammatory cyto-/chemokines, such as IL8 TNF, cell migration pancreatic Ca(2+) responses. Via its enzymatic activity, increases intracellular levels ADP-ribose,...
Nicotinamide phosphoribosyltransferase (Nampt) inhibitors such as FK866 are potent of NAD(+) synthesis that show promise for the treatment different forms cancer. Based on Nampt upregulation in activated T lymphocytes and preliminary reports lymphopenia treated patients, we have investigated its capacity to interfere with lymphocyte function survival. Intracellular pyridine nucleotides, ATP, mitochondrial function, viability, proliferation, activation markers cytokine secretion were assessed...
Abstract Purpose: Histone deacetylases (HDAC) modulate gene transcription and chromatin assembly by modifying histones at the posttranscriptional level. HDAC inhibitors have promising antitumor activity are presently explored in clinical studies. Cumulating evidence animal models of immune disorders also suggests immunosuppressive properties for these small molecules, although underlying mechanisms remain present poorly understood. Here, we evaluated effects two currently use, sodium...
Nicotinamide phosphoribosyltransferase (Nampt) is a key enzyme for nicotinamide adenine dinucleotide (NAD(+)) biosynthesis, and recent evidence indicates its role in inflammatory processes. Here, we investigated the potential effects of pharmacological Nampt inhibition with FK866 mouse myocardial ischemia/reperfusion model. In vivo ex procedures were performed.Treatment reduced infarct size, neutrophil infiltration, reactive oxygen species (ROS) generation within infarcted hearts model...
Aberrant histone deacetylase (HDAC) activity is frequent in human leukemias. However, while classical, NAD+-independent HDACs are an established therapeutic target, the relevance of NAD+-dependent (sirtuins) leukemia treatment remains unclear. Here, we assessed antileukemic sirtuin inhibitors and NAD+-lowering drug FK866, alone combination with traditional HDAC inhibitors. Primary cells, cell lines, healthy leukocytes hematopoietic progenitors were treated (sirtinol, cambinol, EX527) or...
Summary Pharmacological treatments targeting CXC chemokines and the associated neutrophil activation recruitment into atherosclerotic plaques hold promise for treating cardiovascular disorders. Therefore, we investigated whether FK866, a nicotinamide phosphoribosyltransferase (NAMPT) inhibitor with anti-inflammatory properties that recently found to reduce ischaemic myocardium, would exert beneficial effects in mouse atherosclerosis model. Atherosclerotic plaque formation was induced by...
Proteasome inhibitors possess potent antitumor activity against a broad spectrum of human malignancies. However, the effects these compounds on immune system still have to be clearly determined. In present study, we investigated proteasome dendritic cells (DC), antigen-presenting playing key role in initiation responses. Exposure bortezomib, MG132 or epoxomicin was found promote apoptosis monocyte-derived DC and reduce yield viable when given monocytes early during differentiation DC. via...
Abstract Purpose: Bcl-2 overexpression is frequently detected in lymphoid malignancies, being associated with poor prognosis and reduced response to therapy. Here, we evaluated whether affects the cytotoxic activity of proteasome inhibitors taken alone or association conventional anticancer drugs tumor necrosis factor–related apoptosis-inducing ligand (TRAIL). Experimental Design: Jurkat cells engineered overexpress were treated (MG132, epoxomicin, bortezomib), (etoposide doxorubicin),...
Neutrophil function was studied in several patients with recurrent infections, mainly of the skin. Twelve showed impairment neutrophil functions, either chemotaxis or bacterial killing and phagocytosis. Levamisole given four cases: improvement long-lasting clinical remission occurred three them, whilst fourth drug not tolerated. Ascorbic acid administered to other patients, satisfactory remission.
The nicotinamide phosphoribosyltransferase (NAMPT) inhibitor, APO866, has been previously shown to have antileukemic activity in preclinical models, but its cytotoxicity primary leukemia cells is frequently limited. success of current treatments reduced by the occurrence multidrug resistance, which, turn, mediated membrane transport proteins, such as P-glycoprotein-1 (Pgp). Here, we evaluated effects APO866 combination with Pgp inhibitors and studied mechanisms underlying interaction between...
Antibody-dependent cellular cytotoxicity (ADCC) against Raji cells was used as a model system to investigate the polymorphonuclear leukocyte (PMN) mechanisms involved in tumor cell lysis. PMN killed target by nonoxidative means, indicated following observations: 1) from patients with chronic granulomatous disease (CGD), defective their metabolic burst, lysed normally; 2) impairment of oxidative metabolism normal phenylbutazone did not affect ADCC. Rosenthal's inhibitor phospholipase A2...