Search results for "Dox"
showing 10 items of 1345 documents
Human leukocyte elastase counteracts matrix metalloproteinase-7 induced apoptosis resistance of tumor cells.
2008
Matrix metalloproteinase-7 (MMP-7/Matrilysin) is a component of the tumor microenvironment associated with malignant progression. Its expression in tumors protects tumor cells from CD95-mediated apoptosis and the cytotoxic activity of tumor specific CD8(+) T cells. In the present study, we show that human leukocyte elastase (HLE) secreted by polymorphonuclear leukocytes cleaves MMP-7 resulting in loss of enzymatic activity. The anti-apoptotic effect of MMP-7 is reduced in the presence of HLE for CD95-, doxorubicin- and CTL-mediated apoptosis. Our data indicates that HLE may be a natural inactivator of MMP-7 which can counteract MMP-7-induced apoptosis resistance.
Lysosomal alterations in heart and liver of mice treated with doxorubicin.
1985
This study was carried out to evaluate the influence of long-term treatment with doxorubicin (DXR) (4mg/kg IV for 5 weeks) on heart and liver lysosomes of mice. We evaluated the variations in both total and "sedimentable" enzyme activity of cathepsin D, which is the major endopeptidase of myocites and probably involved in physiologic and pathologic degradation of actomyosin and mitochondria, and that of acid phosphatase, which is more prominent in interstitial cells. Our results show that marked changes occur in both total and sedimentable enzyme activity of cathepsin D in the heart of treated animals and to a lesser extent in the liver. In contrast, no modification of either total or sedim…
Composition as identity and plural Cantor's theorem
2016
In this paper, I argue that the thesis of Composition as Identity blocks the plural version of Cantor’s Theorem, and that this in turn has implications for our use of Cantor’s theorem in metaphysics. As an example, I show how this result blocks a recent argument by Hawthorne and Uzquiano, and might be turned around to become an abductive argument for Composition as Identity
0131 : Impact of overweight on anthracycline and trastuzumab-induced cardiotoxicity: experimental study in mice
2015
Trastuzumab (TRZ), a humanized monoclonal antibody against Human Epidermal Growth Factor Receptor 2 (HER2) oncogene, is believed to potentiate doxorubicin (DOX) cardiotoxicity, resulting in left ventricular dysfunction. Few data indicate that overweight could influence DOX-induced cardiotoxicity, and no study has already evaluated the impact of moderate overweight on the cardiotoxic effect of DOX alone or in combination with TRZ. Immediately after birth, litters of C57BL/6 mice were either maintained at 10 (normal litter, NL), or reduced to 3 (small litter, SL) in order to induce programming of ~15% overweight through postnatal overfeeding. At 4 months, in order to evaluate the potentiation…
Dystrophin-deficiency increases the susceptibility to doxorubicin-induced cardiotoxicity
2007
Background and aim: The clinical use of doxorubicin (DOX) and other anthracyclines is limited by a dosage-dependent cardiotoxicity, which can lead to cardiomyopathy. The role of the individual genetic makeup in this disorder is poorly understood. Alterations in genes encoding cardiac cytoskeleton or sarcolemma proteins may increase the susceptibility to doxorubicin-related cardiotoxicity. Methods: Female dystrophin-deficient mice (MDX) and age-matched wild-type mice underwent chronic treatment with doxorubicin. Cardiac function and tissue damage were assessed by echocardiography and histopathology, respectively. Gene expression changes were investigated using microarrays. Results: DOX treat…
Doxorubicin induces wide-spread transcriptional changes in the myocardium of hearts distinguishing between mice with preserved and impaired cardiac f…
2021
Abstract Aims Doxorubicin (DOX) is an important drug for the treatment of various tumor entities. However, the occurrence of heart failure limits its application. This study investigated differential gene expression profiles in the left and right ventricles of DOX treated mice with either preserved or impaired myocardial function. We provide new mechanistic insights into the pathophysiology of DOX-induced heart failure and have discovered pathways that counteract DOX-induced cardiotoxicity. Main methods We used in total 48 male mice and applied a chronic low dose DOX administration (5 mg/kg per injection, in total 20 mg/kg over 4 weeks) to induce heart failure. Echocardiographic parameters …
Iron overload does not potentiate doxorubicin induced cardiotoxicity in vivo in mice and in vitro in cardiomyocytes cell cultures
2013
Background: Doxorubicin (DOX), an anticancer anthracycline, is known to induce serious cardiotoxicity, which is believed to be mediated by oxidative stress and complex interactions with iron. However, the relations between iron metabolism and DOX-induced cardiotoxicity remain a matter of controversy. Methods: Firstly, we used an in vivo murine model of iron overloading (IO) where male C57BL/6 mice received during 3 weeks (D0-D20) a daily dextran-iron injection (15 mg/kg/day.) and then (D21) a single dose of 6 mg/kg DOX. We evaluated cardiac function with echocardiography, myocardial gene's expression, nitro-oxidative stress levels and iron status. Secondly, the anti-proliferative activity o…
Inorganic Nitrate Therapy Improves Doxorubicin-Induced Cardiomyopathy
2011
The anthracycline doxorubicin (DOX) is a potent and effective antineoplastic antibiotic agent widely used in the treatment of a broad range of forms of cancer. The clinical use of DOX is limited by cardiotoxicity, which increases dose dependently and may lead to dilated cardiomyopathy and clinical
C022 Experimental approaches of oxidative stress and cardiotoxicity associated with anthracyclines administration
2009
The chronic cardiotoxicity of anthracyclines anticancer drugs is one of the main factors which limits their prolonged use. Clinically, this cardiotoxicity results in a cardiomyopathy with irreversible congestive heart failure with high mortality. The molecular mechanisms, which could explain this cardiac toxicity, are complex but seem distinct from the anticancer mechanism. Several hypotheses were advanced, but it appears that the production of reactive oxygen and nitrogen species (RONS) constitutes the common denominator.In a first study, we evaluated the acute effect of epirubicin administration on the evolution of cardiac functional parameters and production of RONS. Isolated perfused ra…
Nanoparticle Assembly of Surface-Modified Proteins
2016
Nature's biomaterials such as peptides and proteins represent a valuable source of highly defined macromolecules. Herein we developed a nanoparticle drug delivery system based on the assembly of surface-modified proteins that can be transferred into organic solvents and represent the structural material of the carrier system. The particles are prepared by an oil-in-water nanoemulsion technique without the need of additional denaturation or cross-linking steps for stabilization. We achieve the necessary lipophilic solubility switch of the protein material by high surface PEGylation under conservation of the native three-dimensional protein structure. This study focuses on lysozyme as model e…