A5074689955- Cancer-related Molecular Pathways
- Microtubule and mitosis dynamics
- RNA and protein synthesis mechanisms
- Cystic Fibrosis Research Advances
- Epigenetics and DNA Methylation
- Ocular Oncology and Treatments
- Genomic variations and chromosomal abnormalities
- Advanced biosensing and bioanalysis techniques
- Bacterial Genetics and Biotechnology
- Cancer Genomics and Diagnostics
- Diet and metabolism studies
- Diabetes Treatment and Management
- DNA Repair Mechanisms
- DNA and Nucleic Acid Chemistry
- RNA modifications and cancer
- Autoimmune and Inflammatory Disorders Research
- Cancer, Hypoxia, and Metabolism
- CRISPR and Genetic Engineering
- Click Chemistry and Applications
- Inhalation and Respiratory Drug Delivery
- Epilepsy research and treatment
- RNA Interference and Gene Delivery
- Pharmacological Effects and Toxicity Studies
- Adolescent and Pediatric Healthcare
- Phytochemicals and Antioxidant Activities
University of Palermo
2015-2025
Duke University
2024
Alberta Children's Hospital
2021
University of Calgary
2021
University of Turin
2018
University of Liège
2008-2010
Ospedali Riuniti di Ancona
1992
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...
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...
Primary Immunodeficiency Diseases (PIDs) are associated with multiple genetic alterations including mutations of the LPS responsive Beige anchor (LRBA) gene. Nonsense in LRBA gene resulting premature termination codons cause loss protein expression PID. We evaluated impact a translational readthrough-inducing drug (TRID) ataluren as nonsense suppression therapy PID patient homozygous stop codon mutation exon 30 LRBA. A precision medicine approach allowed us to pass from "in silico" vitro"...
Maxillofacial trauma constitutes one of the significant public health issues globally owing to its multifactorial etiology, ramifications, and socioeconomic burden on world care. This article systematically reviews maxillofacial injury epidemiology, prevention, economic effect, complications. The cause such injuries is varied with road traffic accidents, inter-personal violence, occupational hazards being major contributors globally. In particular, prevention strategies, safety, violence...
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...
Ataluren was reported to suppress nonsense mutations by promoting the readthrough of premature stop codons, although its mechanism action (MOA) is still debated. The likely interaction with CFTR-mRNA has been previously studied molecular dynamics. In this work we extended modeling Ataluren's MOA complementary computational approaches such as induced fit docking (IFD), quantum polarized ligand (QPLD), MM-GBSA free-energy calculations, and mutagenesis. addition CFTR-mRNA, study considered...
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...
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...
The purpose of the present study was to evaluate impact long-term honey ingestion on metabolic disorders and neurodegeneration in mice fed a high-fat diet (HFD). Three groups were with standard (STD), HFD or supplemented (HFD-H) for 16 weeks. Biochemical, histological, Western blotting, RT-PCR Profiler PCR array performed assess parameters, peripheral central insulin resistance neurodegeneration. Daily intake prevented HFD-induced glucose dysmetabolism. In fact, it reduced plasma fasting...
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...
Aurora-A is a centrosome-associated serine/threonine kinase that overexpressed in multiple types of human tumors. Primarily, functions centrosome maturation and mitotic spindle assembly. Overexpression induces amplification G2/M cell cycle progression. Recently, it was observed overexpression renders cells resistant to cisplatin (CDDP)-, etoposide-, paclitaxel-induced apoptosis. Our results indicate already initial stages cancer progression could have major role inducing supernumerary...
Cystic fibrosis (CF) patients develop a severe form of the disease when cystic transmembrane conductance regulator (CFTR) gene is affected by nonsense mutations. Nonsense mutations are responsible for presence premature termination codon (PTC) in mRNA, creating lack functional protein. In this context, translational readthrough-inducing drugs (TRIDs) represent promising approach to correct basic defect caused PTCs. By using computational optimization and biological screening, we identified...