Search results for "Toxicity"
showing 10 items of 2261 documents
Subacute effects of ozone exposure on cultivated human respiratory mucosa.
2001
This study was designed to investigate subacute effects of long-term exposure of both healthy and chronically inflamed human respiratory mucosa to ozone. Functional and metabolic effects on ciliary beat frequency (CBF), release of interleukin 8 (IL-8), interleukin 4 (IL-4), and γ interferon (g-INF), as well as cellular viability and cytotoxicity, were monitored. Cell cultures of 60 specimens (healthy mucosa: n = 30, inflamed mucosa: n = 30) were exposed to synthetic air and to ozone-enriched synthetic air in different concentrations of WO, 500, and WOO μg/m3. Continuous expositions were performed using an air/liquid interface cell culture technique for a period of 4 weeks. CBF was monitore…
Molecular chaperones in the brain endothelial barrier: neurotoxicity or neuroprotection?
2019
Brain microvascular endothelial cells (BMECs) interact with astrocytes and pericytes to form the blood-brain barrier (BBB). Their compromised function alters the BBB integrity, which is associated with early events in the pathogenesis of cancer, neurodegenerative diseases, and epilepsy. Interestingly, these conditions also induce the expression of heat shock proteins (HSPs). Here we review the contribution of major HSP families to BMEC and BBB function. Although investigators mainly report protective effects of HSPs in brain, contrasted results were obtained in BMEC, which depend both on the HSP and on its location, intra- or extracellular. The therapeutic potential of HSPs must be scrupulo…
Mechanisms of NK Cell Activation and Clinical Activity of the Therapeutic SLAMF7 Antibody, Elotuzumab in Multiple Myeloma
2018
Multiple myeloma (MM) is a bone marrow plasma cell neoplasm and is the second most-common hematologic malignancy. Despite advances in therapy, MM remains largely incurable. Elotuzumab is a humanized IgG1 monoclonal antibody targeting SLAMF7, which is highly expressed on myeloma cells, and the antibody is approved for the treatment of relapsed and/or refractory (RR) MM in combination with lenalidomide and dexamethasone. Elotuzumab can stimulate robust antibody-dependent cellular cytotoxicity (ADCC) through engaging with FcγRIIIA (CD16) on NK cells and antibody-dependent cellular phagocytosis (ADCP) by macrophages. Interestingly, SLAMF7 is also expressed on cytolytic NK cells, which also expr…
Molecular strategies to increase yeast iron accumulation and resistance.
2018
All eukaryotic organisms rely on iron as an essential micronutrient for life because it participates as a redox-active cofactor in multiple biological processes. However, excess iron can generate reactive oxygen species that damage cellular macromolecules. The low solubility of ferric iron at physiological conditions increases the prevalence of iron deficiency anemia. A common strategy to treat iron deficiency consists of dietary iron supplementation. The baker’s yeast Saccharomyces cerevisiae is used as a model eukaryotic organism, but also as a feed supplement. In response to iron deficiency, the yeast Aft1 transcription factor activates cellular iron acquisition. However, when constituti…
Gut microbiota and cancer: How gut microbiota modulates activity, efficacy and toxicity of antitumoral therapy
2019
Gut microbiota is involved in gastrointestinal carcinogenesis. Also, it modulates the activity, efficacy and toxicity of several chemotherapy agents, such as gemcitabine, cyclophosphamide, irinotecan, cisplatin and 5-Fluorouracil, and target therapy, such as tyrosine kinase inhibitors. More recently, accumulating data suggest that the composition of gut microbiota may also affect efficacy and toxicity of cancer immunotherapy. Therefore, the manipulation of gut microbiota through antibiotics, probiotics, prebiotics or fecal transplantation has been investigating with the aim to improve efficacy and mitigate toxicity of anticancer drugs.
Trichomonicidal and parasite membrane damaging activity of bidesmosic saponins from Manilkara rufula.
2017
The infection caused by Trichomonas vaginalis is the most common but overlooked non-viral sexually transmitted disease worldwide. Treatment relies on one class of drugs, the 5-nitroimidazoles, but resistance is widespread. New drugs are urgently needed. We reported the effect of crude and purified saponin fractions of Manilkara rufula against Trichomonas vaginalis. The compound responsible for antitrichomonal activity was isolated and identified as an uncommon bidesmosic saponin, Mi-saponin C. This saponin eliminated parasite viability without toxicity against the human vaginal epithelial line (HMVII). In addition, the isolated saponin fraction improved the metronidazole effect against a me…
Cytotoxicity of seven naturally occurring phenolic compounds towards multi-factorial drug-resistant cancer cells
2016
Abstract Introduction In medical oncology, multi-drug resistance (MDR) of cancer cells continues to be a major impediment. We are in quest of novel anti-proliferative agents to overcome drug-resistant tumor cells. Methods In the present study, we investigated the cytotoxicity of 7 naturally occurring phenolic compounds including two isoflavonoids alpinumisoflavone ( 1 ) and laburnetin ( 2 ), one biflavonoid amentoflavone ( 3) , three lignans pycnanthulignene A ( 4 ), pycnanthulignene B ( 5 ), and syringaresinol ( 7 ) and one xanthone, euxanthone ( 6 ) against 9 drug-sensitive and MDR cancer cell lines. The resazurin reduction assay was used to evaluate the cytotoxicity of these compounds, w…
Characterization of the first-in-class T-cell-engaging bispecific single-chain antibody for targeted immunotherapy of solid tumors expressing the onc…
2015
abstract The fetal tight junction molecule claudin 6 (CLDN6) is virtually absent from any normal tissue, whereas it is aberrantly and frequently expressed in various cancers of high medical need. We engineered 6PHU3, a T-cell-engaging bispecific single chain molecule (bi-(scFv)2) with anti-CD3/anti-CLDN6 specificities, and characterized its pharmacodynamic properties. Our data show that upon engagement by 6PHU3, T cells strongly upregulate cytotoxicity and activation markers, proliferate and acquire an effector phenotype. 6PHU3 exerts potent killing of cancer cells in vitro with EC50 values in the pg/mL range. Subcutaneous xenograft tumors in NSG mice engrafted with human PBMCs are eradicat…
Nanoparticle decoration impacts airborne fungal pathobiology
2018
Airborne fungal pathogens, predominantly Aspergillus fumigatus, can cause severe respiratory tract diseases. Here we show that in environments, fungal spores can already be decorated with nanoparticles. Using representative controlled nanoparticle models, we demonstrate that various nanoparticles, but not microparticles, rapidly and stably associate with spores, without specific functionalization. Nanoparticle-spore complex formation was enhanced by small nanoparticle size rather than by material, charge, or "stealth" modifications and was concentration-dependently reduced by the formation of environmental or physiological biomolecule coronas. Assembly of nanoparticle-spore surface hybrid s…
Fasting regulates EGR1 and protects from glucose- and dexamethasone-dependent sensitization to chemotherapy
2017
Fasting reduces glucose levels and protects mice against chemotoxicity, yet drugs that promote hyperglycemia are widely used in cancer treatment. Here, we show that dexamethasone (Dexa) and rapamycin (Rapa), commonly administered to cancer patients, elevate glucose and sensitize cardiomyocytes and mice to the cancer drug doxorubicin (DXR). Such toxicity can be reversed by reducing circulating glucose levels by fasting or insulin. Furthermore, glucose injections alone reversed the fasting-dependent protection against DXR in mice, indicating that elevated glucose mediates, at least in part, the sensitizing effects of rapamycin and dexamethasone. In yeast, glucose activates protein kinase A (P…