A5017641442- Cancer-related Molecular Pathways
- Microtubule and mitosis dynamics
- RNA and protein synthesis mechanisms
- CRISPR and Genetic Engineering
- DNA Repair Mechanisms
- Epigenetics and DNA Methylation
- Genomic variations and chromosomal abnormalities
- Ocular Oncology and Treatments
- Advanced biosensing and bioanalysis techniques
- Cystic Fibrosis Research Advances
- Genomics and Chromatin Dynamics
- RNA regulation and disease
- RNA modifications and cancer
- Chromosomal and Genetic Variations
- Cancer Genomics and Diagnostics
- Bacterial Genetics and Biotechnology
- DNA and Nucleic Acid Chemistry
- RNA Interference and Gene Delivery
- Animal Genetics and Reproduction
- Cancer, Hypoxia, and Metabolism
- Ubiquitin and proteasome pathways
- Carcinogens and Genotoxicity Assessment
- Genetics and Neurodevelopmental Disorders
- Cancer-related gene regulation
- Inhalation and Respiratory Drug Delivery
University of Palermo
2015-2025
Istituto Zooprofilattico Sperimentale Della Sicilia
2007-2023
Centro di Riferimento Oncologico
2012
National Research Council
2010
Salk Institute for Biological Studies
1993-1994
The tumor suppressor p53 is a cell cycle checkpoint protein that contributes to the preservation of genetic stability by mediating either G1 arrest or apoptosis in response DNA damage. Recent reports suggest causes growth through transcriptional activation cyclin-dependent kinase (Cdk)-inhibitor Cip1. Here, we characterize p53-dependent several normal human diploid fibroblast (NDF) strains and p53-deficient lines treated with 0.1-6 Gy gamma radiation. damage progression analyses showed NDF...
Cells with a functional p53 pathway undergo G0/G1 arrest or apoptosis when treated gamma radiation many chemotherapeutic drugs. It has been proposed that DNA damage is the exclusive signal triggers response. However, we found certain ribonucleotide biosynthesis inhibitors caused p53-dependent G0 early G1 in absence of replicative synthesis detectable normal human fibroblasts. CTP, GTP, UTP depletion alone was sufficient to induce arrest. In contrast response damage, characterized by...
Abstract Background Aneuploidy is a hallmark of most human cancers that arises as consequence chromosomal instability and it frequently associated with centrosome amplification. Functional inactivation the Retinoblastoma protein (pRb) has been indicated cause promoting well However, underlying molecular mechanism still remains to be clarified. Results Here we show pRb depletion both in wild type p53 knockout HCT116 cells was presence multipolar spindles, anaphase bridges, lagging chromosomes...
The presence in the mRNA of premature stop codons (PTCs) results protein truncation responsible for several inherited (genetic) diseases. A well-known example these diseases is cystic fibrosis (CF), where approximately 10% (worldwide) patients have nonsense mutations CF transmembrane regulator (CFTR) gene. PTC124 (3-(5-(2-fluorophenyl)-1,2,4-oxadiazol-3-yl)-benzoic acid), also known as Ataluren, a small molecule that has been suggested to allow PTC readthrough even though its target yet be...
Development of distant metastases involves a complex multistep biological process termed the invasion-metastasis cascade, which includes dissemination cancer cells from primary tumor to secondary organs. NOTCH developmental signaling plays critical role in promoting epithelial-to-mesenchymal transition, stemness, and metastasis. Although all four receptors show oncogenic properties, unique each these sequential stepwise events that typify cascade remains elusive. We have established...
Abstract Background Incorrect segregation of whole chromosomes or parts chromosome leads to aneuploidy commonly observed in cancer. The correct centrosome duplication, assuring assembly a bipolar mitotic spindle, is essential for fidelity and preventing aneuploidy. Alteration p53 pRb functions by expression HPV16-E6 E7 oncoproteins has been associated with amplification. However, these last findings could be the result targeting cellular proteins addition HPV16-E7 oncoprotein. To get more...
Nonsense mutations in the CFTR gene are responsible for approximately 8 % of cystic fibrosis (CF) cases worldwide. The consequent premature termination translation leads to production a truncated and non-functional protein. Despite intensive research field, these patients cannot benefit from specific approved therapies yet. To address this issue, study we evaluated potential therapeutic strategy overcome nonsense G542X (UGG > UGA) mutation CFF-16HBEge human bronchial epithelial cells by...
Abstract Background Genetic instability is a hallmark of tumours and preneoplastic lesions. The predominant form genome in human cancer chromosome (CIN). CIN characterized by chromosomal aberrations, gains or losses whole chromosomes (aneuploidy), it often associated with centrosome amplification. Centrosomes control cell division forming bipolar mitotic spindle play an essential role the maintenance stability. However, whether amplification could directly cause aneuploidy not fully...
Abstract Background Changes in chromosome number or structure as well supernumerary centrosomes and multipolar mitoses are commonly observed human tumors. Thus, centrosome amplification mitotic checkpoint dysfunctions believed possible causes of chromosomal instability. The Retinoblastoma tumor suppressor ( RB ) participates the regulation synchrony between DNA synthesis duplication it is involved transcription some genes. Primary fibroblasts were transfected transiently with short...
Background: Induced senescence could be exploited to selectively counteract the proliferation of cancer cells and target them for senolysis. We examined cellular induced by curcumin whether it targeted fisetin quercetin, flavonoids with senolytic activity. Methods: Cell-cycle profiles, chromosome number structure, heterochromatin markers were evaluated via flow cytometry, metaphase spreads, immunofluorescence, respectively. The activation p21waf1/cip1 was assessed RT-qPCR immunoblotting....
Aneuploidy has been acknowledged as a major source of genomic instability in cancer, and it is often considered the result chromosome segregation errors including those caused by defects genes controlling mitotic spindle assembly, centrosome duplication cell-cycle checkpoints. chromosomal also correlated with epigenetic alteration, however molecular basis this correlation poorly understood.To address functional connection existing between changes aneuploidy, we used RNA-interference to...
The spindle assembly checkpoint (SAC) is a cellular surveillance mechanism that ensures faithful chromosome segregation during mitosis and its failure can result in aneuploidy. Previously, it was suggested reduction of the MAD2 gene, encoding major component SAC, induced aneuploidy human tumor cells. However, cell lines contain multiple mutations might affect or exacerbate response to Mad2 depletion. Thus, scenario resulting by depletion primary cells could be different more complex one...
// Giuseppe Costa 1,* , Viviana Barra Laura Lentini 1 Danilo Cilluffo and Aldo Di Leonardo 1,2 Dipartimento di Scienze e Tecnologie Biologiche, Chimiche Farmaceutiche (STEBICEF), Università degli Studi Palermo, Italy 2 Centro OncoBiologia Sperimentale (COBS), * These authors have contributed equally to this study Correspondence to: Leonardo, email: Keywords : DNA demethylation, 5-aza-2'-deoxycytidine (DAC), aneuploidy, chromosome methylation pattern, Chromosome Section Received July 20, 2015...
Cystic Fibrosis (CF) is an autosomal recessive genetic disease caused by mutations in the CFTR gene, coding for chloride channel. About 10% of gene are “stop” that generate a premature termination codon (PTC), thus synthesizing truncated protein. A way to bypass PTC relies on ribosome readthrough, which ribosome’s capacity skip PTC, generating full-length “TRIDs” molecules exerting readthrough; some, mechanism action still under debate. We investigate possible (MOA) our recently synthesized...
Highly Expressed in Cancer protein 1 (Hec1) is a subunit of the Ndc80 complex, constituent mitotic kinetochore. HEC1 has been shown to be over-expressed many cancers, suggesting that up-regulation involved generation and/or maintenance tumour phenotype. However, regulation Hec1 expression normal and cells molecular alterations promoting accumulation this cancer are still unknown. Here we show elevated levels characteristic transformed cell lines different origins kinetochore recruitment also...
The readthrough of nonsense mutations by small molecules like Ataluren is considered a novel therapeutic approach to overcome the gene defect in several genetic diseases as cystic fibrosis (CF). This pharmacological suppresses translation termination at premature codons (PTCs readthrough) thus restoring expression functional protein. However, might be limited nonsense-mediated mRNA decay (NMD), cell process that reduces amount/level PTCs containing mRNAs. Here we investigate combined action...
Retinoblastoma (Rb) is the most common intraocular malignant tumour in childhood, with an incidence of 1 15,000 live births. Complete information on this rare can be easily accessed through internet, although many aspect concerning aetiology and pathogenesis disease, are still controversial. The "two hit" theory, formulated 1971 to explain variegated clinical expression based idea that single gene mutation may determine development cancer. However, view does not take into account recent...