A5048339741- Chronic Myeloid Leukemia Treatments
- Chronic Lymphocytic Leukemia Research
- Cancer Genomics and Diagnostics
- PARP inhibition in cancer therapy
- Genetic factors in colorectal cancer
- Acute Lymphoblastic Leukemia research
- Colorectal Cancer Treatments and Studies
- Lymphoma Diagnosis and Treatment
- Biochemical and Molecular Research
- Eosinophilic Disorders and Syndromes
- HER2/EGFR in Cancer Research
- Breast Cancer Treatment Studies
- Acute Myeloid Leukemia Research
- Lung Cancer Treatments and Mutations
- Cell death mechanisms and regulation
- Molecular Biology Techniques and Applications
- Cholinesterase and Neurodegenerative Diseases
- Cancer Cells and Metastasis
- Ubiquitin and proteasome pathways
- Alzheimer's disease research and treatments
- PI3K/AKT/mTOR signaling in cancer
- Hematopoietic Stem Cell Transplantation
- Colorectal Cancer Surgical Treatments
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- RNA Interference and Gene Delivery
University of Genoa
2013-2024
Ospedale Policlinico San Martino
2009-2024
Institut Jules Bordet
2017
Istituti di Ricovero e Cura a Carattere Scientifico
2012-2015
Hiroshima University
2008
University of Tübingen
2004
Merrimack Pharmaceuticals (United States)
2004
Massachusetts Institute of Technology
2004
Center for Cancer Research
2004
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...
SQLE encodes squalene epoxidase, a key enzyme in cholesterol synthesis. has sporadically been reported among copy-number driven transcripts multi-omics cancer projects. Yet, its functional relevance never subjected to systematic analyses. Here, we assessed the correlation of copy number (CN) and gene expression (GE) across multiple types, focusing on clinico-pathological associations breast (BC). We then investigated whether any biological effect inhibition could be observed BC cell line...
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...
Abstract Multifocal breast cancer ( MFBC ), defined as multiple synchronous unilateral lesions of invasive cancer, is relatively frequent and has been associated with more aggressive features than unifocal cancer. Here, we aimed to investigate the genomic heterogeneity between sharing similar histopathological parameters. Characterization different from 36 patients ductal involved identification non‐silent coding mutations in 360 protein‐coding genes (171 tumour matched normal samples). We...
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...
Background Chronic cardiotoxicity is less common in male than female patients receiving doxorubicin and other anthracyclines at puberty adolescence. We hypothesized that this sex difference might be secondary to distinct activities of hormones on cardiomyocyte senescence, which thought central the development long‐term anthracycline cardiomyopathy. Methods Results H9c2 cells neonatal mouse cardiomyocytes were exposed with or without prior incubation testosterone 17β‐estradiol, main androgen...
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...
Mutations of the presenilin 1 (PS1) gene are most common cause early onset familial Alzheimer disease (FAD). PS1 mutations alter activity gamma-secretase on beta-amyloid precursor protein (APP), leading to selective overproduction (Abeta) 42 peptides, species that forms oligomers may exert toxic effects neurons. Here we show mutations, expressed both transiently and stably, in non-neuronal neuronal cell lines increase expression beta-secretase (BACE1), rate-limiting step Abeta production....
Background Previous studies have provided a comprehensive picture of genomic alterations in primary and metastatic Hormone Receptor (HR)-positive, Human Epidermal growth factor 2 (HER2)-negative breast cancer (HR+ HER2- BC). However, the evolution landscape HR+ BC during adjuvant endocrine therapies (ETs) remains poorly investigated. Methods findings We performed characterization surgically resected patients relapsing or at completion ET. Using customized panel, we comprehensively evaluated...
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...
Large independent analyses on cancer cell lines followed by functional studies have identified Schlafen 11 (SLFN11), a putative helicase, as the strongest predictor of sensitivity to DNA-damaging agents (DDAs), including platinum. However, its role prognostic biomarker is undefined, partially due lack validated methods score SLFN11 in human tissues. Here, we implemented pipeline quantify samples. By analyzing cohort high-grade serous ovarian carcinoma (HGSOC) specimens before platinum-based...
The efficacy of anti-HER2 therapeutics, such as lapatinib and trastuzumab, is limited by primary acquired resistance. Cellular adaptations that allow breast cancer cell to survive prolonged HER2 inhibition include de-repression the transcription factor FOXO3A with consequent estrogen receptor activation, and/or increased HER3 signaling. Here, we used low-density arrays, quantitative PCR, western blotting determine how signaling or PI3K inhibitors affects expression genes involved in...
Senescence and apoptosis are two distinct cellular programs that activated in response to a variety of stresses. Low or high doses the same stressor, i.e., anticancer drug doxorubicin, may either induce senescence, respectively, cardiac muscle cells. We have demonstrated PPARδ, ligand-activated transcriptional factor controls lipid metabolism, insulin sensitivity inflammation, is also involved doxorubicin-induced senescence program. This occurs through its interference with repressor protein...
Standard treatment for locally advanced rectal adenocarcinoma (LARC) includes a combination of chemotherapy with pyrimidine analogues, such as capecitabine, and radiation therapy, followed by surgery. Currently no clinically useful genomic predictors benefit from neoadjuvant chemoradiotherapy (nCRT) exist LARC. In this study we assessed the expression 8,127 long noncoding RNAs (lncRNAs), poorly studied in LARC, to infer their ability classifying patients' pathological complete response...
Lapatinib, a dual HER2 and EGFR tyrosine kinase inhibitor is highly active in HER2+ breast cancer. However, its efficacy limited by either primary or acquired resistance. Although mutations ras genes are rarely found cancer, H-ras overexpression frequently observed. Moreover, genetic alterations that do not directly involve such as Brk amplification, ultimately result increased signaling. Using SKBR3 cells, cancer cell line naturally devoid of PI3KCA, PTEN, BRAF, we show both expression an...