Biomedical subjects

Luca Ronconi

Publications and source records attributed to Luca Ronconi.

5 recordsLinked to original sources

PubMed2026

Predicting training outcomes for developmental dyslexia from EEG data.

Developmental dyslexia (DD) is characterised by lower-than-average reading abilities and is diagnosed in approximately 10% of individuals. The societal barriers may limit professional fulfilment and psychological wellbeing of individuals with DD, calling for the development of effective interventions to counteract them. As DD is associated with challenges in both phonological and visuo-attentional domains, different longitudinal training approaches were developed to strengthen them. However, they require a considerable amount of personal, social and economic resources and the outcomes may vary depending on individual differences in behavioural and neurophysiological functionality. Hence, predicting training outcomes might help in developing personalised treatment protocols and optimising the use of resources. In the present work we applied machine learning to resting-state EEG to predict longitudinal training outcomes in adults with DD enrolled in a randomized clinical trial. In particular, one group received a visuo-attentional training combined with transcranial alternating current stimulation (tACS), another group received visuo-attentional training with sham/placebo stimulation, and the third group received a phonological training with sham/placebo stimulation. The improvement in text reading speed was associated with spectral power in low-beta and individual frequencies in the alpha (IAF) and beta (IBF) bands, while the improvement in pseudoword reading was associated with IBF. The findings highlight the potential of capturing neural markers of treatment responsiveness in DD. Future studies should focus on the generalisability of predictive models to real-world settings, while investigating whether specific EEG markers predict responsiveness to distinct remediation protocols, thus supporting the development of personalised interventions.

Humans↗

PubMed2006

A novel anticancer gold(III) dithiocarbamate compound inhibits the activity of a purified 20S proteasome and 26S proteasome in human breast cancer cell cultures and xenografts.

Although cisplatin has been used for decades to treat human cancer, some toxic side effects and resistance are observed. It has been suggested that gold(III) complexes, containing metal centers isoelectronic and isostructural to cisplatin, are promising anticancer drugs. Gold(III) dithiocarbamate complexes were shown to exhibit in vitro cytotoxicity, comparable with and even greater than cisplatin; however, the involved mechanism of action remained unknown. Because we previously reported that copper(II) dithiocarbamates are potent proteasome inhibitors, we hypothesized that gold(III) dithiocarbamate complexes could suppress tumor growth via direct inhibition of the proteasome activity. Here, for the first time, we report that a synthetic gold(III) dithiocarbamate (compound 2) potently inhibits the activity of a purified rabbit 20S proteasome and 26S proteasome in intact highly metastatic MDA-MB-231 breast cancer cells, resulting in the accumulation of ubiquitinated proteins and the proteasome target protein p27 and induction of apoptosis. The compound 2-mediated proteasome inhibition and apoptosis induction were completely blocked by addition of a reducing agent DTT or N-acetyl-L-cysteine, showing that process of oxidation is required for proteasome inhibition by compound 2. Treatment of MDA-MB-231 breast tumor-bearing nude mice with compound 2 resulted in significant inhibition of tumor growth, associated with proteasome inhibition and massive apoptosis induction in vivo. Our findings reveal the proteasome as a primary target for gold(III) dithiocarbamates and support the idea for their potential use as anticancer therapeutics.

Acetylcysteine↗

PubMed2006

Gold(III) dithiocarbamate derivatives for the treatment of cancer: solution chemistry, DNA binding, and hemolytic properties.

Gold(III) compounds are emerging as a new class of metal complexes with outstanding cytotoxic properties and are presently being evaluated as potential antitumor agents. We report here on the solution and electrochemical properties, and the biological behavior of some gold(III) dithiocarbamate derivatives which have been recently proved to be one to 4 orders of magnitude more cytotoxic in vitro than the reference drug (cisplatin) and to be able to overcome to a large extent both intrinsic and acquired resistance to cisplatin itself. Their solution properties have been monitored in order to study their stability under physiological conditions; remarkably, they have shown to undergo complete hydrolysis within 1 h, the metal center remaining in the +3 oxidation state. Their DNA binding properties and ability in hemolyzing red blood cells have been also evaluated. These gold(III) complexes show high reactivity toward some biologically important isolated macromolecules, resulting in a dramatic inhibition of both DNA and RNA synthesis and inducing DNA lesions with a faster kinetics than cisplatin. Nevertheless, they also induce a strong and fast hemolytic effect (compared to cisplatin), suggesting that intracellular DNA might not represent their primary or exclusive biological target.

Animals↗

PubMed2005

Gold dithiocarbamate derivatives as potential antineoplastic agents: design, spectroscopic properties, and in vitro antitumor activity.

At present, cisplatin (cis-diamminodichloroplatinum(II)) is one of the most largely employed anticancer drugs as it is effective in the treatment of 70-90% of testicular and, in combination with other drugs, of ovarian, small cell lung, bladder, brain, and breast tumors. Anyway, despite its high effectiveness, it exhibits some clinical problems related to its use in the curative therapy, such as a severe normal tissue toxicity (in particular, nephrotoxicity) and the frequent occurrence of initial and acquired resistance to the treatment. To obtain compounds with superior chemotherapeutic index in terms of increased bioavailability, higher cytotoxicity, and lower side effects than cisplatin, we report here on some gold(I) and gold(III) complexes with dithiocarbamate ligands (DMDT = N,N-dimethyldithiocarbamate; DMDTM = S-methyl-N,N-dimethyldithiocarbamate; ESDT = ethylsarcosinedithiocarbamate), which have been synthesized, purified, and characterized by means of elemental analyses, conductivity measurements, mono- and bidimensional NMR, FT-IR, and UV-vis spectroscopy, and thermal analyses. Moreover, the electrochemical properties of the designed compounds have been studied through cyclic voltammetry. All the synthesized gold complexes have been tested for their in vitro cytotoxic activity. Remarkably, most of them, in particular gold(III) derivatives of N,N-dimethyldithiocarbamate and ethylsarcosinedithiocarbamate, have been proved to be much more cytotoxic in vitro than cisplatin, with IC50 values about 1- to 4-fold lower than that of the reference drug, even toward human tumor cell lines intrinsically resistant to cisplatin itself. Moreover, they appeared to be much more cytotoxic also on the cisplatin-resistant cell lines, with activity levels comparable to those on the corresponding cisplatin-sensitive cell lines, ruling out the occurrence of cross-resistance phenomena and supporting the hypothesis of a different antitumor activity mechanism of action.

Antineoplastic Agents↗

PubMed2005

Synthesis, characterization, and comparative in vitro cytotoxicity studies of platinum(II), palladium(II), and gold(III) methylsarcosinedithiocarbamate complexes.

This work reports on the synthesis, characterization, and in vitro cytotoxic activity of some new platinum(II), palladium(II), and gold(III) derivatives of methylsarcosinedithiocarbamate and its S-methyl ester, to study their behavior as potential antitumor agents. The biological activity of these compounds, as determined by growth inhibition and apoptosis induction, has been investigated in both human leukemic promyelocites HL60 and human squamous cervical adenocarcinoma HeLa cell lines, and their activity has been compared to the well-known platinum-based anticancer agent cisplatin. On the basis of these experimental results, [Pd(MSDT)X]n (MSDT = methylsarcosinedithiocarbamate; X = Cl, Br) complexes show a strong dose-dependent growth inhibition of both HL60 and HeLa cells, with IC(50) values slightly higher than those recorded for cisplatin; moreover, [Au(MSDT)X(2)] activity appears significantly higher or, at least, comparable to that of the reference drug. Exposure of both cell lines to [Pd(MSDT)X]n and [Au(MSDT)X(2)] complexes induces apoptosis, as determined by an Apo2.7 assay.

Antineoplastic Agents↗