Search results for "Doxorubicin"
showing 8 items of 298 documents
Inhibition of Rac1 signaling by lovastatin protects against anthracycline-induced cardiac toxicity
2011
Normal tissue damage limits the efficacy of anticancer therapy. For anthracyclines, the clinically most relevant adverse effect is cardiotoxicity. The mechanisms involved are poorly understood and putative cardioprotectants are controversially discussed. Here, we show that the lipid-lowering drug lovastatin protects rat H9c2 cardiomyoblasts from doxorubicin in vitro. Protection by lovastatin is related to inhibition of the Ras-homologous GTPase Rac1. It rests on a reduced formation of DNA double-strand breaks, resulting from the inhibition of topoisomerase II by doxorubicin. Doxorubicin transport and reactive oxygen species are not involved. Protection by lovastatin was confirmed in vivo. I…
Rac1 protein signaling is required for DNA damage response stimulated by topoisomerase II poisons.
2012
To investigate the potency of the topoisomerase II (topo II) poisons doxorubicin and etoposide to stimulate the DNA damage response (DDR), S139 phosphorylation of histone H2AX (γH2AX) was analyzed using rat cardiomyoblast cells (H9c2). Etoposide caused a dose-dependent increase in the γH2AX level as shown by Western blotting. By contrast, the doxorubicin response was bell-shaped with high doses failing to increase H2AX phosphorylation. Identical results were obtained by immunohistochemical analysis of γH2AX focus formation, comet assay-based DNA strand break analysis, and measuring the formation of the topo II-DNA cleavable complex. At low dose, doxorubicin activated ataxia telangiectasia m…
Rho GTPases Are Involved in the Regulation of NF-κB by Genotoxic Stress
2001
A common cellular response to genotoxic agents and inflammatory cytokines is the activation of NF-kappaB. Here, we addressed the question of whether small GTPases of the Rho family are involved in the stimulation of NF-kappaB signaling by genotoxic agents or TNFalpha in HeLa cells. Inhibition of isoprenylation of Rho proteins by use of the HMG-CoA reductase inhibitor lovastatin attenuated UV-, doxorubicin-, and TNFalpha-induced degradation of IkappaBalpha as well as drug-stimulated DNA binding activity of NF-kappaB. Furthermore, NF-kappaB-regulated gene expression stimulated by either UV irradiation or treatment with TNFalpha was abrogated by lovastatin pretreatment. This indicates that iso…
Development of New Targeted Inulin Complex Nanoaggregates for siRNA Delivery in Antitumor Therapy.
2021
Here, a novel strategy of formulating efficient polymeric carriers based on the already described INU-IMI-DETA for gene material whose structural, functional, and biological properties can be modulated and improved was successfully investigated. In particular, two novel derivatives of INU-IMI-DETA graft copolymer were synthesized by chemical functionalisation with epidermal growth factor (EGF) or polyethylenglycol (PEG), named INU-IMI-DETA-EGF and INU-IMI-DETA-PEG, respectively, in order to improve the performance of already described “inulin complex nanoaggregates” (ICONs). The latter were thus prepared by appropriately mixing the two copolymers, by varying each component from 0 to 100 wt%…
Effects of ectopic expression of NGAL on doxorubicin sensitivity.
2012
Neutrophil gelatinase-associated lipocalin (NGAL, a.k.a Lnc2) is a member of the lipocalin family which has diverse roles including stabilizing matrix metalloproteinase-9 from auto-degradation and as siderocalins which are important in the transport of iron. NGAL also has important biological functions involved in immunity and inflammation as well as responses to kidney damage. NGAL expression has also been associated with certain neoplasia and is important in the metastasis of breast cancer. Many advanced cancer patients have elevated levels of NGAL in their urine and it has been proposed that NGAL may be a prognostic indicator for certain cancers (e.g. breast, brain, and others). NGAL exp…
A fluorescence study of the loading and time stability of doxorubicin in sodium cholate/PEO-PPO-PEO triblock copolymer mixed micelles
2019
Abstract Hypothesis Doxorubicin hydrochloride (DX) is one of the most powerful anticancer agents though its clinical use is impaired by severe undesired side effects. DX encapsulation in nanocarrier systems has been introduced as a mean to reduce its toxicity. Micelles of the nonionic triblock copolymers of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO) (PEO-PPO-PEO), are very promising carrier systems. The positive charge of DX confines the drug to the hydrophilic corona region of the micelles. The use of mixed micelles of PEO-PPO-PEO copolymers and a negatively charged bile salt should favour the solubilization of DX in the apolar core region of the micelles. Experiments We st…
Estudio farmacogenético del tratamiento del cáncer de mama basado en antraciclinas y taxanos
2016
Existe una importante variabilidad interindividual en la respuesta a los medicamentos que condiciona que no sea fácil predecir la efectividad o seguridad de un fármaco en un paciente concreto. La Farmacogenética (PGt) estudia el vínculo entre las variaciones en la secuencia de ADN de un paciente y su respuesta al tratamiento farmacológico. La variación de un único nucleótido puede tener consecuencias dramáticas, de modo que la identificación de variantes que alteren la función o expresión de las proteínas implicadas en la farmacocinética o farmacodinamia y su efecto final sobre la respuesta es el objetivo de la PGt. El Cáncer de Mama (CM) es el tipo de cáncer más frecuente en mujeres. A pes…
Biodegradable Metal-Organic Framework-Based Microrobots (MOFBOTs).
2020
Microrobots and metal–organic frameworks (MOFs) have been identified as promising carriers for drug delivery applications. While clinical applications of microrobots are limited by their low drug loading efficiencies and the poor degradability of the materials used for their fabrication, MOFs lack motility and targeted drug delivery capabilities. The combination of these two fields marks the beginning of a new era; MOF‐based small‐scale robots (MOFBOTs) for biomedical applications. Yet, biodegradability is a major hurdle in the field of micro‐ and nanoswimmers including small‐scale robots. Here, a highly integrated MOFBOT that is able to realize magnetic locomotion, drug delivery, and selec…