Search results for "toxicity."
showing 10 items of 2180 documents
The hard road to data interpretation: 3 or 6 months of adjuvant chemotherapy for patients with stage III colon cancer?
2019
Background Six months of adjuvant oxaliplatin-based chemotherapy is standard for patients with stage III colon cancer following surgery. However, oxaliplatin is associated with peripheral neurotoxicity which worsens over treatment duration. Consequently, a shorter treatment duration, if equally effective, would be extremely beneficial. A pooled analysis of data for 12 834 stage III colon cancer patients, from six randomised phase III trials of adjuvant therapy, the International Duration Evaluation of Adjuvant chemotherapy study, was carried out and the results presented at the ASCO Annual Meeting 2017. To clarify the potential impact of these results on clinical practice, ESMO decided to s…
Association of 5-FU Therapeutic Drug Monitoring to DPD Phenotype Assessment May Reduce 5-FU Under-Exposure
2020
In order to limit 5-fluorouracil (5-FU) toxicity, some health agencies recommend evaluating dihydropyrimidine dehydrogenase (DPD) deficiency before any 5-FU treatment introduction. In our study, we investigated relationships between 5-FU clearance and markers of DPD activity such as uracilemia (U), dihydrouracilemia (UH2)/U ratio, or genotype of the gene encoding DPD (DPYD). All patients with gastrointestinal cancers who received 5-FU-based regimens form March 2018 to June 2020 were included in our study. They routinely benefited of a pre-therapeutic DPYD genotyping and phenotyping. During 5-FU infusion, blood samples were collected to measure 5-FU steady-state concentration in order to ada…
Immunotherapeutic properties of chemotherapy
2017
IF 5.363; International audience; Impressive remissions driven by immunological checkpoint blockade in cancer patients have prompted the scientific community to investigate afresh the crosstalk between cancer cells and the patient's immune system. Preclinical and clinical studies have highlighted that the anticancer efficacy of some conventional chemotherapeutics is based on their ability to restore anticancer immune responses. The current challenge is to understand and circumvent immune resistance mechanisms to chemo- and immunotherapies to design relevant immunotherapy and chemotherapy combinations. In this review, we will summarize which immunological processes are involved in the antica…
Cardiotoxicity and Cardioprotection by Artesunate in Larval Zebrafish
2019
Although artesunate (ART) is generally accepted as a safe and well-tolerated first-line treatment of severe malaria, cases of severe side effects and toxicity of this compound are also documented. This study applied larval zebrafishes to determine the acute toxicity and efficacy of ART and performed RNA-sequencing analyses to unravel the underlying signaling pathways contributing to ART’s activities. Results from acute toxicity assay showed that a single-dose intravenous injection of ART from 3.6 ng/fish (1/9 maximum nonlethal concentration) to 41.8 ng/fish (lethal dose 10%) obviously induced pericardial edema, circulation defects, yolk sac absorption delay, renal edema, and swim bladder l…
Use of Early Life-Stages of Zebrafish to Assess Toxicity of Sediments Contaminated by Organotin Compounds
2016
ABSTRACTThis study examined the response of early life-stages (ELS) of zebrafish to organotin-contaminated sediment from Lake Huruslahti (HL) in Central Finland. A dilution series (0, 10, 33, and 100%) of the native (HL) and the sediment spiked with tributyltin (TBT) determined a dose-response of zebrafish ELS to organotin-contaminated sediment. Sediment elutriates were assessed by bacterial bioluminescence assay and microscopical pathologies of 1–3 days post-fertilization zebrafish (1–3dpfZF). Brain aromatase (cyp19a1b) and tissue vitellogenin (vtg1) were assayed from early-juvenile zebrafish (20dpfZF) exposed to intact sediment. In vivo modulation of cyp19a1b and vtg1 transcripts in 20dpf…
Citrus sinensis and Vitis vinifera Protect Cardiomyocytes from Doxorubicin-Induced Oxidative Stress: Evaluation of Onconutraceutical Potential of Veg…
2020
Abstract: The interest towards nutraceuticals able to counteract drug side effects is continuously growing in current chemotherapeutic protocols. In the present study, we demonstrated that smoothies containing mixtures of Citrus sinensis and Vitis vinifera L. cv. Aglianico N, two typical fruits of the Mediterranean diet, possess bioactive polyphenols that protect cardiomyocytes against doxorubicin-induced oxidative stress. The polyphenolic extracts isolated from Citrus sinensis- and Vitis vinifera-based functional smoothies were deeply characterized by Liquid Chromatography-Mass Spectrometry methods. Subsequently, the functional smoothies and relative mixtures were tested to verify their ab…
Tryptophan-Containing Dual Neuroprotective Peptides: Prolyl Endopeptidase Inhibition and Caenorhabditis elegans Protection from β-Amyloid Peptide Tox…
2018
Neuroprotective peptides represent an attractive pharmacological strategy for the prevention or treatment of age-related diseases, for which there are currently few effective therapies. Lactoferrin (LF)-derived peptides (PKHs) and a set of six rationally-designed tryptophan (W)-containing heptapeptides (PACEIs) were characterized as prolyl endopeptidase (PEP) inhibitors, and their effect on β-amyloid peptide (Aβ) toxicity in a Caenorhabditis elegans model of Alzheimer’s disease (AD) was evaluated. Two LF-derived sequences, PKH8 and PKH11, sharing a W at the C-terminal end, and the six PACEI heptapeptides (PACEI48L to PACEI53L) exhibited significant in vitro PEP inhibition. The inhibitory pe…
In Vivo Cardiotoxicity Induced by Sodium Aescinate in Zebrafish Larvae
2016
Sodium aescinate (SA) is a widely-applied triterpene saponin product derived from horse chestnut seeds, possessing vasoactive and organ-protective activities with oral or injection administration in the clinic. To date, no toxicity or adverse events in SA have been reported, by using routine models (in vivo or in vitro), which are insufficient to predict all aspects of its pharmacological and toxicological actions. In this study, taking advantage of transparent zebrafish larvae (Danio rerio), we evaluated cardiovascular toxicity of SA at doses of 1/10 MNLC, 1/3 MNLC, MNLC and LC10 by yolk sac microinjection. The qualitative and quantitative cardiotoxicity in zebrafish was assessed at 48 h p…
Modulating disease-relevant tau oligomeric strains by small molecules
2020
The pathological aggregation of tau plays an important role in Alzheimer's disease and many other related neurodegenerative diseases, collectively referred to as tauopathies. Recent evidence has demonstrated that tau oligomers, small and soluble prefibrillar aggregates, are highly toxic due to their strong ability to seed tau misfolding and propagate the pathology seen across different neurodegenerative diseases. We previously showed that novel curcumin derivatives affect preformed tau oligomer aggregation pathways by promoting the formation of more aggregated and nontoxic tau aggregates. To further investigate their therapeutic potential, we have extended our studies o disease-relevant bra…
Evaluation of the protein and bioactive compound bioaccessibility/bioavailability and cytotoxicity of the extracts obtained from aquaculture and fish…
2020
Bioavailability, bioaccessibility, bioactivity and cytotoxicity define if a bioactive compound obtained from aquaculture and associated by-products can be assimilated and used for the body in a safe and efficient way. Four models are used to evaluate the bioavailability: in vitro (simulated gastrointestinal digestion using intestinal epithelial Caco-2 cell cultures); ex vivo (gastrointestinal organs or organoids in laboratory conditions); in situ (intestinal perfusion in animals) and in vivo (animal studies and human studies). In vitro models are very effective, predicting in vivo actions since they evaluate multiple conditions regardless physiological effects. However, in vivo systems are …