5,022 research outputs found
NBN Gene Polymorphisms and Cancer Susceptibility: A Systemic Review. * di Masi A. and Antoccia A. are co-corresponding authors of this work.
No full textThe relationship between DNA repair failure and cancer is well established as in the case of rare, high penetrant genes in high cancer risk families. Beside this, in the last two decades, several studies have investigated a possible association between low penetrant polymorphic variants in genes devoted to DNA repair pathways and risk for developing cancer. This relationship would be also supported by the observation that DNA repair processes may be modulated by sequence variants in DNA repair genes, leading to susceptibility to environmental carcinogens. In this framework, the aim of this review is to provide the reader with the state of the art on the association between common genetic variants and cancer risk, limiting the attention to single nucleotide polymorphisms (SNPs) of the NBN gene and providing the various odd ratios (ORs). In this respect, the NBN protein, together with MRE11 and RAD50, is part of the MRN complex which is a central player in the very early steps of sensing and processing of DNA double-strand breaks (DSBs), in telomere maintenance, in cell cycle control, and in genomic integrity in general. So far, many papers were devoted to ascertain possible association between common synonymous and non-synonymous NBN gene polymorphisms and increased cancer risk. However, the results still remain inconsistent and inconclusive also in meta-analysis studies for the most investigated E185Q NBN miscoding variant
Metabolism and Pharmacological Characterization at μ-, κ-, and δ- Opioid Receptors Using a Novel Non-Radioactive Assay of Nitazenes and Methadone-like Synthetic Opioids
No full textI nuovi oppioidi sintetici (NSO), inclusi i nitazeni e i derivati della difenilmetilpiperidina, rappresentano sfide significative per la salute pubblica a causa della loro elevata potenza, rapida diffusione e limitata caratterizzazione. Questo studio mira a migliorare la comprensione del loro metabolismo e della loro attività farmacologica, fornendo strumenti essenziali per il rilevamento e la valutazione del rischio. Utilizzando epatociti primari umani e microsomi epatici umani e analisi LC-HRMS/MS, abbiamo caratterizzato il metabolismo in vitro e in vivo di etonitazepipne, dipianone, protonitazepine e metonitazepine. Un’analisi approfondita dei dati, supportata da software predittivi, ha permesso l’identificazione delle principali vie metaboliche e biomarcatori.
La caratterizzazione farmacologica di questi composti si è concentrata sulla loro attivazione dei recettori oppioidi μ-, κ- e δ- (MOR, KOR e DOR). È stato sviluppato e ottimizzato un saggio ad alta capacità basato su HTRF® per il legame del GTP Gi, per valutarne la potenza e l’efficacia. Come previsto, etonitazepipne, protonitazepine e metonitazepine hanno condiviso, come principali trasformazioni metaboliche, l’O-dealchilazione, l’idrossilazione e l’apertura del gruppo pirrolidinico o piperidinico in acido butanoico. Il dipianone ha mostrato un profilo metabolico unico, con metaboliti principali generati dopo l’apertura del pirrolidinico in butanolo e acido butanoico, seguita da ciclizzazione.
Grazie al saggio HTRF® basato sul legame GTP Gi, il protonitazepine è risultato il più potente ed efficace agonista del MOR, con una potenza circa 6 volte superiore al fentanyl, seguita da etonitazepipne, metonitazepine e dipianone. Questa ricerca fornisce informazioni fondamentali sul metabolismo e sulla farmacologia degli NSO, proponendo biomarcatori unici di consumo e un nuovo saggio HTRF® rapido e semplice per lo studio dell’attività dei recettori.Novel Synthetic Opioids (NSOs), including nitazenes and diphenylmethylpiperidine derivatives, pose significant challenges to public health due to their high potency, rapid emergence, and limited characterization. This study aims to advance the understanding of their metabolism and pharmacological activity, providing essential tools for detection and risk assessment. Using cryopreserved primary human hepatocytes, Pooled Human Liver Microsomes and LC-HRMS/MS analysis, we characterized the in vitro and in vivo metabolism of etonitazepipne, dipyanone, protonitazepyne, and metonitazepyne. Comprehensive data mining supported by predictive software enabled the identification of key metabolic pathways and biomarkers. The pharmacological characterization of these compounds focused on their activation of the μ-, κ-, and δ-opioid receptors (MOR, KOR, and DOR). A high-throughput HTRF®-based GTP Gi binding assay was developed and optimized to assess their potency and efficacy.
As expected, etonitazepipne, protonitazepyne and metonitazepyne shared as main transformation O-dealkylation, hydroxylation and pyrrolidine or piperidine opening to butanoic acid. Dipyanone presented a unique metabolic profile, and the main metabolites were generated after pyrrolidine opening to butanol and butanoic acid followed by cyclisation. As a result of the HTRF®-based GTP Gi binding assay, protonitazepyne was the most potent and efficacious agonist at MOR, resulting around 6 times more potent than fentanyl, followed by etonitazepipne, metonitazepyne and dipyanone. This research provides critical insights into the metabolism and pharmacology of NSOs, proposing unique biomarkers of consumption and a novel, fast and easy HTRF®-based GTP Gi binding assay for receptor activity study
Targeting telomerase and telomeres to enhance ionizing radiation effects in in vitro and in vivo cancer models
No full textOne of the hallmarks of cancer consists in the ability of tumor cells to divide indefinitely, and to maintain stable telomere lengths throughout the activation of specific telomere maintenance mechanisms (TMM). Therefore in the last fifteen years, researchers proposed to target telomerase or telomeric structure in order to block limitless replicative potential of cancer cells providing a fascinating strategy for a broad-spectrum cancer therapy.In the present review, we report in vitro and in vivo evidence regarding the use of chemical agents targeting both telomerase or telomere structure and showing promising antitumor effects when used in combination with ionizing radiation (IR). RNA interference, antisense oligonucleotides (e.g., GRN163L), non-nucleoside inhibitors (e.g., BIBR1532) and nucleoside analogs (e.g., AZT) represent some of the most potent strategies to inhibit telomerase activity used in combination with IR. Furthermore, radiosensitizing effects were demonstrated also for agents acting directly on the telomeric structure such as G4-ligands (e.g., RHPS4 and Telomestatin) or telomeric-oligos (T-oligos). To date, some of these compounds are under clinical evaluation (e.g., GRN163L and KML001).Advantages of Telomere/Telomerase Targeting Compounds (T/TTCs) coupled with radiotherapy may be relevant in the treatment of radioresistant tumors and in the development of new optimized treatment plans with reduced dose adsorbed by patients and consequent attenuation of short- end long-term side effects. Pros and cons of possible future applications in cancer therapy based on the combination of T/TCCs and radiation treatment are discussed
Comparison between two FISH techniques in the in vitro study of cytogenetic markers for low-dose X-ray exposure in human primary fibroblasts.
No full textTelomere loss, not average telomere length, confers radiosensitivity to TK6-irradiated cells
No full text""Many and varied are the proposed mechanisms that lead to resistance to ionizing radiation treatment. Among them, an inverse relationship between telomere length and radioresistance has been recently advanced. Investigating such a relationship in TK6 lymphoblasts, we found that clones originating from cells survived to 4Gy of X-rays showed a significantly higher telomere length when compared with clones grown from untreated cells. The lengthening observed was not attributable to a radiation-induced increase in telomerase activity, as demonstrated by TRAP assay performed in the dose range of 1-10Gy. Given the evidence that TK6 whole population was characterized by heterogeneity in cellular mean telomere length and telomere loss, we tested the hypothesis that a process of selection may favour cells with longer telomeres (more radioresistant cells) following exposure to irradiation. In order to do this 15 independent TK6 clones were selected and characterized for telomere length and loss on the basis of q-FISH and flow-FISH analysis. Among the screened clones four characterized by long telomeres and four characterized by short telomeres were tested for their radiosensitivity by means of clonogenic assay. The results obtained showed that, in our experimental conditions (cellular model, radiation doses) no significant correlation was observed between radiosensitivity and mean telomere lengths, whereas a positive correlation was observed with respect to telomere loss. Overall, these results indicate that telomere loss and not mean telomere length plays a critical role in the phenomenon of radiosensitivity\\\/radioresistance."
Francesco Scorza Barcellona o della passione agiografica
No full textL'autrice traccia, sul filo dei ricordi, il profilo scientifico ed umano di Francesco Scorza Barcellona ed introduce gli studi raccolti nel volume.The author traces, on the thread of memories, the scientific and human profile of Francesco Scorza Barcelona and introduces the studies collected in the book
Delle lodi di don Francesco Medici de' principi di Toscana : orazione /
No full textEngraved t.p. vignette of Medici arms. On recto of 2nd leaf is Callot's full-page engraved port. of Francesco de' Medici, son of Grand Duke Ferdinand I. It is in Lieure's 1st state. The port. also appeared the same year in Alessandro Adimari's Esequie dell' ill.mo & ecc.mo principe don Francesco Medici (Florence : Gio. Donato & Bernardino Giunti); see Lieure. Large woodcut Giunti device on p. [31].Lieure, J. Jacques Callot,Mode of access: Internet.At head of front pastedown is bookplate of Francesco Riccardi de Vernaccia (Florence, ca. 1780; see Gelli, p. 387). Below it is the label of Horatius (Orazio) Landau, with stamped shelfmark 53021. At foot is the bookplate of U. Manganelli, signed with the initials SER. A dedicatory inscription at foot of t.p. has been scratched out.Binding: modern marbled paper, backed in green vellum. Date, author & title writte on spine.Port. trimmed into the image at right margin and foot
The G4 ligand RHPS4 induces chromosomal instability and increases sensitivity to X-rays in glioblastoma cells.
No full textFrankenstein
No full text@inproceedings{orsini2015graph,
title={Graph invariant kernels},
author={Orsini, Francesco and Frasconi, Paolo and De Raedt, Luc},
booktitle={IJCAI Proceedings-International Joint Conference on Artificial Intelligence. IJCAI},
year={2015}
New insight in penile cancer
No full textPenile cancer is a rare disease. Most of penile cancer are squamous cell carcinoma. Diagnosis is based on self-examination, clinical examination and confirmatory biopsy. Several imaging techniques could be used for staging purposes. However, the best modality for staging in intermediate and high-risk patients is by surgical evaluation and the use of inguinal lymph node dissection, that has also a therapeutic effect. Unfortunately, inguinal lymph node dissection is underused. Penile cancer treatment may have a major adverse impact on urinary and sexual function and on quality of life. Penile-sparing surgery and radiation therapies are available, and in selected patients offer good outcomes with acceptable rates of local recurrence. Penile-sparing surgery should be preferred when indicated. Follow-up with periodical controls is mandatory up to 5 years. However, risk of local, nodal and distant recurrence after 5 years was reported. Imaging is not routinely recommended during follow-up. Patients should be trained to self-examination during the follow-up
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