A5003285597- Neurofibromatosis and Schwannoma Cases
- Computational Drug Discovery Methods
- Chemical Synthesis and Analysis
- Synthesis and Biological Evaluation
- Sarcoma Diagnosis and Treatment
- Neuroblastoma Research and Treatments
- Synthesis and Reactions of Organic Compounds
- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- Nicotinic Acetylcholine Receptors Study
- Synthesis and Characterization of Heterocyclic Compounds
- Biochemical and Molecular Research
- Click Chemistry and Applications
- Fluorine in Organic Chemistry
- Genomics and Rare Diseases
- Multicomponent Synthesis of Heterocycles
- Graphene research and applications
- Meningioma and schwannoma management
- Chemical Reaction Mechanisms
- Ethics in Clinical Research
- Soft tissue tumor case studies
- Microbial Natural Products and Biosynthesis
- Neurological disorders and treatments
- Receptor Mechanisms and Signaling
- Ion-surface interactions and analysis
Kidney Cancer Association
2024
Children's Tumor Foundation
2016-2021
Siena Biotech (Italy)
2009-2015
Istituto Nazionale per la Fisica della Materia
2006
University of Catania
1991-2006
Elettra-Sincrotrone Trieste S.C.p.A.
2005
University of Strathclyde
2001-2003
International Union of Pure and Applied Chemistry
2002
Centro Siciliano di Fisica Nucleare e di Struttura della Materia
1991
A modified one-phonon confinement model is developed for the calculation of micro-Raman spectra in Si nanocrystals, permitting simultaneous determination Raman frequency, intensity, and linewidth. Using a specific spatial correlation function phonon dispersion relations, are calculated under limitations imposed on wave vector by confinement. Results obtained as nanocrystal size range $1.2--100\phantom{\rule{0.3em}{0ex}}\mathrm{nm}$. The frequency shift line broadening compared with...
Neurofibromatosis Type 2 (NF2) is an autosomal dominant genetic syndrome caused by mutations in the NF2 tumor suppressor gene resulting multiple schwannomas and meningiomas. There are no FDA approved therapies for these tumors their relentless progression results high rates of morbidity mortality. Through a combination throughput screens, preclinical vivo modeling, evaluation kinome en masse , we identified actionable drug targets efficacious experimental therapeutics treatment related These...
National and international public–private partnerships, consortia, government initiatives are underway to collect share genomic, personal, healthcare data on a massive scale. Ideally, these efforts will contribute the creation of medical information commons (MIC), comprehensive resource that is widely available for both research clinical uses. Stakeholder participation essential in clarifying goals, deepening understanding areas complexity, addressing long-standing policy concerns such as...
Meningiomas are the most common primary brain tumor in adults, and somatic loss of neurofibromatosis 2 (NF2) suppressor gene is a frequent genetic event. There no effective treatment for tumors that recur or continue to grow despite surgery and/or radiation. Therefore, targeted therapies either delay progression cause shrinkage much needed. Our earlier work established mammalian target rapamycin complex mTORC1/mTORC2 activation NF2-deficient meningiomas. High-throughput kinome analyses were...
Neurofibromatosis 2 (NF2) is a rare tumor suppressor syndrome that manifests with multiple schwannomas and meningiomas. There are no effective drug therapies for these benign tumors conventional have limited efficacy. Various model systems been created several targets implicated in NF2-driven tumorigenesis based on known effects of the absence merlin, product NF2 gene. We tested priority compounds biology traditional dose-concentration studies meningioma schwann cell systems. Concurrently,...
Alpha-7 nicotinic acetylcholine receptor (alpha7 nAChR) agonists are promising therapeutic candidates for the treatment of cognitive impairment. We report a series novel, potent small molecule (4-18) alpha7 nAChR deriving from our continuing efforts in areas Alzheimer's disease and schizophrenia. One compounds containing urea moiety (16) was further shown to be selective agonist with excellent vitro vivo profiles, brain penetration, oral bioavailability demonstrated efficacy multiple...
Abstract Neurofibromatosis type 1 (NF1) is a genetic disorder with range of clinical manifestations such as widespread growth benign tumours called neurofibromas, pain, learning disorders, bone deformities, vascular abnormalities and even malignant tumours. With the establishment Children’s Tumour Foundation biobank, neurofibroma samples can now be collected directly from patients to analysed by larger scientific community. This work describes pilot study characterize one class neurofibroma,...
In addition to large plexiform neurofibromas (pNF), NF1 patients are frequently disfigured by cutaneous (cNF) and often afflicted with chronic pain itch even from seemingly normal skin areas. Both pNFs cNF consist primarily of benign hyperproliferating nonmyelinating Schwann cells (nSC). While pNF clearly arise within deep nerves plexuses, the role innervation in origin is unknown. First, we conducted a comprehensive, multi-molecular, immunofluorescence (IF) analyses on 3mm punch biopsies...
The development of a versatile solid phase synthesis bicyclic polyaza heterocycles including pteridines, purines, and deazapurines is described. strategy comprises the linking pre-formed pyrimidine through thioether at 2 or 4 position to polystyrene resin, cyclisation second ring, direct oxidative cleavage product from resin by nucleophilic substitution. This provides not only for substituent variation in but also site cleavage. Limitations scope methodology are set intrinsic reactivity...
In the present paper we report an extended x-ray-absorption fine-structure study of Ar ion implanted in Al and Si matrices. The as-implanted samples show presence crystalline overpressurized clusters at room temperature. Ar-Ar nearest-neighbor distance allows us to estimate overpressure 25 44 kbar exerted on bubbles by matrices, respectively. second- third-coordination-shell signals confirms that precipitates are a phase. Debye temperatures, calculated from Debye-Waller factors, found be...
Cystic fibrosis (CF) is a lethal genetic disease caused by mutations of the gene encoding cystic transmembrane conductance regulator (CFTR) with prevalence ΔF508 mutation. Whereas detailed mechanisms underlying have yet to be fully elucidated, recent breakthroughs in clinical trials demonstrated that CFTR dysfunction can corrected drug-like molecules. On basis this success, screening campaign was carried out, seeking new compounds able rescue ΔF508-CFTR led discovery novel series correctors...
Here, we describe the selection and optimization of a chemical series active in both full-length fragment-based Huntington's disease (HD) assay. Twenty-four thousand small molecules were screened phenotypic HD assay, identifying compounds bearing 3-hydroxy-3-trifluoromethylpyrazole moiety as able to revert toxicity induced by mutant Htt up 50%. A exploration around led identification compound 4f, which demonstrated be Htt171-82Q rat primary striatal neuron assay PC12-Exon-1 based This was...
Modern phenotypic high-throughput screens (HTS) present several challenges including identifying the target(s) that mediate effect seen in screen, characterizing 'hits' with a polypharmacologic target profile, and contextualizing screen data within large space of drugs screening models. To address these challenges, we developed Drug-Target Explorer. This tool allows users to query molecules database experimentally-derived curated compound-target interactions identify structurally similar...
A significant challenge facing rare disease communities is finding a sufficient quantity and variety of data to develop test disease-specific hypotheses. Here we describe an approach sharing in which stakeholders from the neurofibromatosis (NF) research community collaborated disease-focused portal with goal supporting scientists within outside as well clinicians patient advocates.
Huntington's Disease is a rare neurodegenerative disease caused by an abnormal expansion of CAG repeats encoding polyglutamine in the first exon huntingtin gene. N-terminal fragments containing (polyQ) sequences aggregate and can bind to cellular proteins, resulting several pathophysiological consequences for affected neurons such as changes gene transcription. One transcriptional pathway that has been implicated HD pathogenesis CREB binding protein (CBP)/cAMP responsive element (CREB)...
In recent years, medical foundations have become increasingly influential, and now play an instrumental integral role in the research development of their disease area interest. While some directly invested taking drug candidates to clinic, others focused on creating specific tools for accelerating identification effective treatments. Here, we describe a new model, developed by Children's Tumor Foundation ( CTF ), which may rare ecosystem. On one hand, uses its position build bridges between...