Search results for "Toxicity"
showing 10 items of 2261 documents
Role of biomarkers in monitoring antiblastic cardiotoxicity
2016
Early detection of anticancer drug-induced cardiotoxicity (CTX) has been evaluated by most international scientific cardiology and oncology societies. High expectations have been placed on the use of specific biomarkers. In recent years, conventional biomarkers and molecules of more recent interest have been tested and compared in the context of anticancer drug-related CTX. Encouraging results were obtained from studies on molecules of myocardial damage, such as troponin and markers of myocardial wall stress, including circulating natriuretic peptides, as well as from the assessment of the products of inflammation or circulating levels of free radicals. However, clear guidelines on their se…
A recommended practical approach to the management of anthracycline-based chemotherapy cardiotoxicity: an opinion paper of the working group on drug …
2016
Anthracyclines are the mainstay of treatment of a variety of haematological malignancies and solid tumours. Unfortunately, the clinical use of these drugs is limited by cumulative, dose-related cardiotoxicity which may ultimately lead to a severe and irreversible form of cardiomyopathy. Thus, there is an increasing need for close cooperation among cardiologists, oncologists and haemato-oncologists. As anthracyclines save lives, the logical goal of this cooperation, besides preventing or mitigating cardiotoxicity, is to promote an acceptable balance between the potential cardiac side effects and the vital benefit of anticancer treatment. This manuscript, which is specifically addressed to th…
Design, Synthesis and Biological Evaluation of Novel Pyrazolo[1,2,4]triazolopyrimidine Derivatives as Potential Anticancer Agents
2021
Three novel pyrazolo-[4,3-e][1,2,4]triazolopyrimidine derivatives (1, 2, and 3) were designed, synthesized, and evaluated for their in vitro biological activity. All three compounds exhibited different levels of cytotoxicity against cervical and breast cancer cell lines. However, compound 1 showed the best antiproliferative activity against all tested tumor cell lines, including HCC1937 and HeLa cells, which express high levels of wild-type epidermal growth factor receptor (EGFR). Western blot analyses demonstrated that compound 1 inhibited the activation of EGFR, protein kinase B (Akt), and extracellular signal-regulated kinase (Erk)1/2 in breast and cervical cancer cells at concentrations…
Hsp60 Protects against Amyloid β Oligomer Synaptic Toxicity via Modification of Toxic Oligomer Conformation
2019
Alzheimer's disease (AD) is the leading cause of dementia worldwide. While the etiology of AD remains uncertain, neurotoxic effects of amyloid beta oligomers (Aβo) on synaptic function, a well-established early event in AD, is an attractive area for the development of novel strategies to modify or cease the disease's progression. In this work, we tested the protective action of the mitochondrial chaperone Hsp60 against Aβo neurotoxicity, by determining the direct effect of Hsp60 in changing Aβo toxic conformations and thus reducing their dysfunctional synaptic binding and consequent suppression of long-term potentiation. Our data suggest that Hsp60 has a direct impact on Aβo, resulting in a…
Anticancer study of heterobimetallic platinum(II)-ruthenium(II) and platinum(II)-rhodium(III) complexes with bridging dithiooxamide ligand
2019
Abstract Three heterobimetallic platinum (II)/ruthenium (II) and platinum (II)/rhodium (III) complexes, A: Pt{S–S2C2(NR)2H}{μ-S2C2(NR)2}-[Ru (p-cymene)Cl], R = isoamyl; B: Pt{S–S2C2(NR)2H}{μ-S2C2(NR)2}[Rh (phpy)2], R = isoamyl; C: [Pt{S–S2C2(NR)2H}{μ-S2C2(NR)2}-[Rh(C5Me5)Cl]], R = benzyl, were prepared from mononuclear complexes 1 and 2, 1: [Pt (H-isoamyl2DTO)2]; 2: [Pt (H-benzyl2DTO)2], DTO = dithiooxamide, by reaction of 1 or 2 with the corresponding chlorido-bridged dimers, [Rh(C5Me5)Cl (μ-Cl)]2, [Ru (p-cymene)Cl (μ-Cl)]2 or [Rh (phpy)2 (μ-Cl)]2, and then evaluated as anticancer agents for the inhibition of the three proteolytic activities of human 20S proteasome, one of the main target …
A synthetic hexapeptide (Argireline) with antiwrinkle activity
2008
Botulinum neurotoxins (BoNTs) represent a revolution in cosmetic science because of their remarkable and long-lasting antiwrinkle activity. However, their high neurotoxicity seriously limits their use. Thus, there is a need to design and validate non-toxic molecules that mimic the action of BoNTs. The hexapeptide Ac-EEMQRR-NH2 (coined Argireline) was identified as a result of a rational design programme. Noteworthy, skin topography analysis of an oil/water (O/W) emulsion containing 10% of the hexapeptide on healthy women volunteers reduced wrinkle depth up to 30% upon 30 days treatment. Analysis of the mechanism of action showed that Argireline significantly inhibited neurotransmitter relea…
Interaction between 24-hydroxycholesterol, oxidative stress, and amyloid-β in amplifying neuronal damage in Alzheimer’s disease: three partners in cr…
2011
All three cholesterol oxidation products implicated thus far in the pathogenesis of Alzheimer's disease, 7β-hydroxycholesterol, 24-hydroxycholesterol, and 27-hydroxycholesterol, markedly enhance the binding of amyloid-beta (Aβ) to human differentiated neuronal cell lines (SK-N-BE and NT-2) by up-regulating net expression and synthesis of CD36 and β1-integrin receptors. However, only 24-hydroxycholesterol markedly potentiates the pro-apoptotic and pro-necrogenic effects of Aβ(1-42) peptide on these cells: 7β-hydroxycholesterol and 27-hydroxycholesterol, like unoxidized cholesterol, show no potentiating effect. This peculiar behavior of 24-hydroxycholesterol at physiologic concentrations (1 μ…
Photo-inhibition of Ab fibrillation mediated by a newly designed fluorinated oxadiazole
2015
Uncontrolled aggregation of amyloid beta peptide (A?) is the main cause of Alzheimer's Disease. Therapeutic approaches of intervention in amyloid diseases include the use of small molecules able to stabilize the soluble A? conformation, or to redirect the amyloidogenic pathway towards non-toxic and non-fibrillar states. Fluorometric measurements revealed that the 3-(4'-trifluoromethylphenyl)-5-(4'-methoxyphenyl)-1,2,4-oxadiazole, when irradiated, is able to interact with monomeric A? peptide readdressing the aggregation pathway toward the formation of amorphous aggregates as evidenced by means of CD, AFM, and SAXS measurements. We hypothesize that this compound, under radiation, forms a rea…
Polyaspartamide-graft- Polymethacrylate Nanoparticles for Doxorubicin Delivery
2011
A new PHEA-IB-PMANa + copolymer has been synthesized and its pH-induced self-assembly has been investigated in an aqueous medium. PHEA-IB-PMANa + formed nanoparticles with diameters from 25 to 50 nm upon protonation of the carboxylic acid moieties dislocated along the grafted polymethacrylate sodium salt side chains. The physico-chemical characterization of the nanoparticles was performed using light scattering, zeta-potential measurements, SEM, and AFM. Doxorubicin-loaded nanoparticles were prepared and drug release profiles were evaluated under conditions mimicking physiological media. A biological characterization was carried out by testing the cytotoxicity on Caco-2 cells, and cellular …
Solution Properties and Potential Biological Applications of Zwitterionic Poly(ε-N-methacryloyl-l-lysine)
2013
Poly(e-N-methacryloyl-l-lysine) (PMALys) was synthesized by free radical polymerization yielding a zwitterionic polymer with Mw = 721 000 g mol–1. The polymer dissolves in pure water as well as in aqueous salt solution up to 5 M NaClO4 and over wide range of pH values (1.3 ≤ pH ≤ 12.7) as single chains without any sign for aggregate formation. The zwitterionic polymer shows an expanded random coil structure at and close to isoelectric conditions and further expands upon addition of acid and base, respectively. The polymer fulfills four major prerequisites for a promising nano carrier in potential biomedical applications: (1) It is biocompatible, indicated by a low cytotoxicity. (2) It does …