1,531 research outputs found
Small molecule inhibitors of kdm5 histone demethylases increase the radiosensitivity of breast cancer cells overexpressing JARID1B
No full textNHERF1 (Na+/H+ exchanger 3 regulating factor 1) is an integral membrane adaptor protein carrying two NH2-terminal PDZ (postsynaptic density 95/discs large/zona occludens 1) tandem domains.1 PDZ1 (11-97 amino acids) and PDZ2 (150-237 amino acids) show 74% identity to each other and bind to specific carboxyl-terminal motifs on target proteins, such as -catenin and PTEN, that may have a pivotal role in tumorigenesis. Oncogenic activity of NHERF1 is strictly dictated by changes on its subcellular localization.1,2 A pharmacophore model was used to filter out an in-house training set of about 6000 compounds, leading to identify a potent inhibitor of NHERF1.3 We herein reported the design and synthesis of new NHERF1 inhibitors (Figure 1).4 The new compounds were synthesized by treating the appropriate indole with thionyl chloride and the proper amino derivative in the presence of pyridine in dichloromethane at room temperature for 12 h; alternatively, the coupling reaction was carried out using (benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate and triethylamine in N,N-dimethylformamide at room temperature for 12 h. Compounds 5, 9, 10 and 13 exhibited a remarkable cytotoxicity in Ls174TshBeta-Cat cells. The binding to NHERF1 PDZ was confirmed by means of a dansylated peptide corresponding to the C-terminal sequence of Beta2-AR. When used in combination with antagonists of Beta-catenin, the new derivatives increased the apoptotic death of colorectal cancer cells refractory to currently available Wnt/Beta-catenin-targeted agents. References 1. Vaquero, J.; Nguyen Ho-Bouldoires, T. H.; Clapéron, A.; Fouassier, L. Oncogene 2017, 36, 3067‒3079. 2. Georgescu, M. M.; Morales, F. C.; Molina, J. R.; Hayashi, Y. Curr. Mol. Med. 2008, 8, 459−468. 3. Saponaro, C.; Sergio, S.; Coluccia, A.; De Luca, M.; La Regina, G.; Mologni, L.; Famiglini, V.; Naccarato, V.; Bonetti, D.; Gautier, C.; Gianni, S.; Vergara, D.; Salzet, M.; Fournier, I.; Bucci, C.; Silvestri, R.; Gambacorti Passerini, C.; Maffia, M.; Coluccia, A. M. L. Oncogene 2018, 37, 3301‒3316. 4. Coluccia, A.; La Regina, G.; Naccarato, V.; Nalli, M.; Orlando, V.; Biagioni, S.; De Angelis, M. L.; Baiocchi, M.; Gautier, C.; Gianni, S.; Di Pastena, F.; Di Magno, L.; Canettieri, G.; Coluccia, A. M. L.; Silvestri, R. ACS Med. Chem. Lett. 2019, 10, 499‒503
Riflessioni e proposte in margine alla redazione del Lessico Etimologico Italiano; l’utilizzazione delle fonti antiche
No full textLessico Etimologico Italiano. Supplemento bibliografico, a cura di M Pfister, con la collaborazione di R. Coluccia, D. Hauck, H. Hauck, G. Tancke. Analisi, progettazione informatica ed elaborazione dati a cura di M. Linciano, Wiesbaden, Reichert
No full textCytogenetic analysis of the Mediterranean Palinuridae Palinurus elephas and P. mauritanicus (Crustacea, Decapoda).
No full textCytogenetic analysis of the Mediterranean Palinuridae Palinurus elephas and P. mauritanicus (Crustacea, Decapoda)
E. Coluccia, A. Cau, S. Salvadori, R. Cannas, A.M. Deiana
Dipartimento di Biologia Animale ed Ecologia, Università di Cagliari, V.le Poetto, 1- 09126 Cagliari, Italy - email: [email protected]
Palinurus elephas (Fabricius, 1787) and P. mauritanicus Gruvel, 1911 are two Mediterranean spiny lobster species living at different depths.. The knowledge on the karyology of Decapoda are scanty owing to technical constraints in obtaining good chromosomal preparations. To date cytogenetic analysis by chromosome banding are very few. In the contest of a cytogenetic and molecular study on the two Mediterranean Palinuridae we present a characterization of mitotic and meiotic chromosomes of these species by different staining techniques. Chomosomal preparations have been obtained from testicular and somatic tissues by a direct method. Heterochromatin has been localized by C-banding. This technique allowed also a sharp differentiation of chromosomes, a clear identification of meiotic figures and the detection of supernumerary chromosomes in both species. B chromosomes are variable in number, very small, completely heterochromatic and in meiosis I they are often asynaptic. Their presence could account for the variability recorded in determining the chromosome number. The heterochromatin analysis has been deepened by fluorochrome banding. Quinacrine and DAPI localized AT-rich clusters in several centromeric and paracentromeric regions; chromomicin A3 localized GC-rich DNA in centromeric and paracentromeric regions and in some small chromosomes, entirely fluorescent
Treating chronic myeloid leukemia by inhibition of tubulin polymerization
No full textMicrotubules are an attractive target for the development of active anti-leukemia agents (1). Despite some evidence, the therapeutic potential of colchicine site binding agents in chronic myeloid leukemia (CML) has not been adequately explored.
Recently, starting from previously reported aroylindoles (ARIs, e.g. 1) we have developed 3-aroyl-1-arylpyrroles (ARAPs, e.g. 2) via benzocracking approach (Chart 1) (2). Pursuing our studies, we designed and synthesized 3-aroyl-1,4-diarylpyrroles (ARDAPs, 3-16) as potential anticancer agents (3).
ARDAPs exhibited potent inhibition of tubulin polymerization, binding of colchicine to tubulin and cancer cell growth. (4-(4-Aminophenyl)-1-phenyl-1H-pyrrol-3-yl)(3,4,5-trimethoxyphenyl)methanone inhibited the proliferation of BCR/ABL-expressing KU812 and LAMA84 cells from CML patients in blast crisis and of hematopoietic cells ectopically expressing the imatinib mesylate (IM)-sensitive KBM5-WT or its IM-resistant KBM5-T315I mutation. The same compound minimally affected the proliferation of normal blood cells, indicating that it may be a promising agent to overcome broad tyrosine kinase inhibitor resistance in relapsed/refractory CML patients. New ARDAP significantly decreased CML proliferation by inducing G2/M phase arrest and apoptosis via mitochondria-dependent pathway and increased the cytotoxic effects of IM in human CML cells.
References. (1) Yeh, Y.-Y.; Liou, J.-P.; Lee, Y.-L. et al. Invest. New Drugs 2017, 35, 427-435. (2) La Regina, G.; Bai, R.; Coluccia, A. et al. J. Med. Chem. 2014, 57, 6531-6552. (3) La Regina, G.; Bai, R.; Coluccia, A. et al. ACS Med. Chem. Lett. 2017, 8, 521-526
Esiti di lat. adamās / diamas: è mai davvero esistito nell’italoromanzo il significato ‘calamita’?
No full textAttraverso l'analisi lessicografica di due voci tra loro collegate della tradizione lapidaria, adamās e diamas, si dimostra come la verifica filologica delle attestazioni isolate o singolari porti ad un risultato lessicografico complessivamente modificato, che nel caso specifico suggerisce una rilettura e una nuova interpretazione di quattro tra le più antiche liriche italiane
Long-Lasting Nanoscale Wireless Communications with Energy-Harvesting
No full textIl progresso tecnologico innescato dalle nanotecnologie ha recentemente promosso lo sviluppo di nanodispositivi che abilitano differenti nuove promettenti applicazioni in diversi campi. Data la dimensione limitata dei nano-dispositivi, la letteratura scientifica ha introdotto due nuovi paradigmi di comunicazione per la loro interazione: comunicazioni nella banda dei terahertz e comunicazioni molecolari. Tuttavia, la progettazione di schemi di trasmissione di lunga durata (cioè supportati da fonti energetiche rinnovabili) in questo contesto rappresenta ancora un argomento di ricerca inesplorato. Negli ultimi anni, i nanogeneratori piezoelettrici sono emersi come un punto di svolta nella progettazione di schemi di trasmissione basati sulla raccolta di energia su scala nanometrica. Di conseguenza, questa tesi considera la loro adozione nelle comunicazioni elettromagnetiche in banda terahertz e nelle comunicazioni molecolari basate sulla diffusione, proponendo strategie di controllo della potenza in trasmissione basate sulla teoria del controllo in retroazione. Nel dettaglio, la potenza di trasmissione viene impostata dinamicamente in modo proporzionale al budget energetico utilizzando uno schema di controllo ad anello chiuso. Inoltre, per quanto riguarda le comunicazioni molecolari basate sulla libera diffusione, questa tesi propone una nuova metodologia per calcolare il numero di molecole ottimale da rilasciare per ogni frame, garantendo sia la semplicità del processo di trasmissione che i vincoli energetici e i valori di Bit Error Rate predefiniti. A tal fine, la tesi formula anche un problema di ottimizzazione con lo scopo di minimizzare una funzione obiettivo dipendente dalla quantità di energia disponibile e dal numero di pacchetti in coda. Le simulazioni sono state utilizzate per convalidare i modelli analitici formulati, rappresentare il comportamento degli approcci proposti in scenari realistici e dimostrare la capacità unica degli approcci concepiti di garantire il livello di prestazioni previsto.The advance of nanotechnologies recently promoted the development of nanodevices enabling promising applications in different fields. Given the restricted size of nano-devices, the scientific literature introduced two novel communication paradigms for their interaction: terahertz band communications and molecular communications. However, the design of long-lasting transmission schemes (i.e., supported by renewable energy sources) in this context still represents an open research topic. In the last years, piezoelectric nanogenerators emerged as a turning point in the design of energy-aware and energy harvesting transmission schemes at the nanoscale. Accordingly, this thesis considers their adoption in electromagnetic communications in the terahertz band and in diffusion-based molecular communications, proposing power control strategies based on feedback control theory. Here, the transmission power is dynamically set proportionally to the available energy budget by using a closed-loop control scheme. Furthermore, concerning the diffusion-based molecular communications, this thesis proposes a novel methodology for optimally tuning the number of molecules to release on a per-frame basis, while guaranteeing the simplicity of the transmission process, energy constraints and target Bit Error Rate values. To this end, the thesis also formulates an optimization problem willing to minimize an objective function depending on the available energy budget and the number of enqueued packets. Computer simulations are used to validate the formulated analytical models, depict the behavior of the proposed approaches in conceivable scenarios, and demonstrate the unique ability of the conceived approaches to ensure the expected performance level
3-Aroyl-1,4-diarylpyrroles inhibit chronic myeloid leukemia cell growth through an interaction with tubulin
No full textMicrotubules are an attractive target for the development of effective anti-leukemia agents.[1] Evidence has accumulated correlating inhibition of tubulin polymerization and leukemic cell proliferation.[2] The activity of colchicine site agents in chronic myeloid leukemia (CML) has not been adequately explored.
Recently, starting from previously reported aroylindoles (ARI, 1)[3] we developed a class of 3-aroyl-1-arylpyrroles (ARAPs, 2) via benzocracking approach by shifting the indole benzene moiety to position 1 of the pyrrole ring.[4] ARAPs proved to be potent inhibitors of both tubulin assembly and cancer cells growth, by binding the colchicine binding site. Pursuing our studied on tubulin targeting agents, we designed 3-aroyl-1,4-diarylpyrroles (ARDAPs, 3-16) as potential anticancer agents bearing different substituents at the 1- or 4-phenyl ring (Chart 1).
ARDAPs exhibited potent inhibition of tubulin polymerization, binding of colchicine to tubulin and cancer cell growth. (4-(4-Aminophenyl)-1-phenyl-1H-pyrrol-3-yl)(3,4,5-trimethoxyphenyl)methanone inhibited the proliferation of BCR/ABL-expressing KU812 and LAMA84 cells from CML patients in blast crisis and of hematopoietic cells ectopically expressing the imatinib mesylate (IM)-sensitive KBM5-WT or its IM-resistant KBM5-T315I mutation. The same compound minimally affected the proliferation of normal blood cells, indicating that it may be a promising agent to overcome broad tyrosine kinase inhibitor resistance in relapsed/refractory CML patients. New ARDAP significantly decreased CML proliferation by inducing G2/M phase arrest and apoptosis via a mitochondria-dependent pathway and increased the cytotoxic effects of IM in human CML cells.
References. [1] de Bruin, E. C.; Medema, J. P. Cancer Treat. Rev. 2008, 34, 737-749. [2] Bates, D.; Feris, E. J.; Danilov, A. V. et al. Cancer Biol. Ther. 2016, 17, 291-299. [3] La Regina, G.; Sarkar, T.; Bai, R. et al. J. Med. Chem. 2009, 52, 7512-7527. [4] La Regina, G.; Bai, R.; Coluccia, A. et al. J. Med. Chem. 2014, 57, 6531-6552
Migliorini e la storia linguistica del mezzogiorno (con una postilla sulla antica poesia italiana in caratteri ebraici e in caratteri greci), in Bruno Migliorini, l'uomo e il linguista (Rovigo 1896 – Firenze 1975). Atti del convegno di studi. Rovigo, Accademia dei Concordi, 11-12 aprile 2008, a cura di M. Santipolo e M. Viale, Accademia dei Concordi Editore, Rovigo 2009, 183-222.
No full textA partire dai "Testi non toscani" di Migliorini-Folena, si fa un bilancio degli studi recenti di storia linguistica meridionale e pugliese. Si segnala la specificità e la rilevanza dei testi meridionali in caratteri greci e in caratteri ebraici. Si indicano prospettive e desiderat
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