843 research outputs found
S100A12 as diagnostic tool in the differential diagnosis of sJIA associated MAS vs. hereditary or acquired HLH
No full textGeoffrey Cooper LA CELLULA
No full textLo studio della biologia è un compito arduo perchè il campo è molto vasto e in rapida evoluzione, caratterizzato dalla continua esplosione di nuove informazioni
Reaching the threshold: a multilayer pathogenesis of macrophage activation syndrome.
No full textMacrophage activation syndrome (MAS) is a potentially fatal complication of rheumatic diseases. The condition is considered part of secondary hemophagocytic lymphohistiocytoses (HLH). There are similarities in genetic background, pathogenesis, and clinical and laboratory features with primary HLH (p-HLH). We describe findings in mouse models of secondary HLH, comparing them with models of p-HLH and the cellular and molecular mechanisms involved, and relate them to recent findings in patients with secondary HLH. A multilayer model is presented in which background inflammation, infections, and genetics all contribute in different proportions and in several ways. Once the "threshold" has been reached, inflammatory cytokines are the final effectors, independent of the interplay between different upstream pathogenic factors
Nanomaterials as Inhibitors of Epithelial Mesenchymal Transition in Cancer Treatment
No full textEpithelial-mesenchymal transition (EMT) has emerged as a key regulator of cell invasion and metastasis in cancers. Besides the acquisition of migratory/invasive abilities, the EMT process is tightly connected with the generation of cancer stem cells (CSCs), thus contributing to chemoresistance. However, although EMT represents a relevant therapeutic target for cancer treatment, its application in the clinic is still limited due to various reasons, including tumor-stage heterogeneity, molecular-cellular target specificity, and appropriate drug delivery. Concerning this last point, different nanomaterials may be used to counteract EMT induction, providing novel therapeutic tools against many different cancers. In this review, (1) we discuss the application of various nanomaterials for EMT-based therapies in cancer, (2) we summarize the therapeutic relevance of some of the proposed EMT targets, and (3) we review the potential benefits and weaknesses of each approach
Cell-based assays to study ERK pathway/caveolin1 interactions
No full textCaveolin1, the main component of caveolae, plays a major role in regulating cell motility, gene expression, and cytoskeleton remodeling downstream of many membrane receptors. Here, we summarize different techniques set up to study changes in cell morphology and cell motility regulated by ERK/caveolin1 interactions during induction of epithelial mesenchymal transition (EMT) in mesothelial cells (MCs)
Editorial: Autophagy modulation in cancer treatment utilizing nanomaterials and nanocarriers
No full text20.500.12530/8785
Medicament for preventing peritoneal fibrosis due to long term peritoneal dialysis, comprises MEK 1 or 2 activity modulating agent
No full textAbstract: NOVELTY - Peritoneal fibrosis is prevented using an agent for modulating MEK 1 and/or MEK 2 activity.
USE - For preventing or treating fibrosis of the peritoneal membrane, including peritoneal opacification, tanned peritoneal syndrome, mural fibrosis and sclerosing peritonitis syndrome, which results from long-term peritoneal dialysis.
ADVANTAGE - An effective treatment for preventing progressive loss of peritoneal dialytic capacity in patients undergoing peritoneal dialysis.
DETAILED DESCRIPTION - A composition comprising an agent for modulating MEK 1 and/or MEK 2 activity is used to prepare a medicament for preventing or treating peritoneal fibrosis. INDEPENDENT CLAIMS are also included for the following:
(1) Method for identifying therapeutic agents suitable for treating peritoneal fibrosis, comprising contacting the compound to be analyzed with the polynucleotide and/or polypeptide MEK 1 and/or MEK 2 and then detecting the bond between the compound and polynucleotide and/or polypeptide;
(2) Method for identifying therapeutic agents suitable for treating peritoneal fibrosis, comprising measuring the activity of MEK 1 and/or MEK 2 at a given concentration of the compound to be analyzed or in the absence of this compound, and measuring the same activity at different concentration of this compound;
(3) Method for identifying therapeutic agents suitable for treating peritoneal fibrosis, comprising measuring the activity of MEK 1 and/or MEK 2 at a given concentration of the compound to be analyzed, and measuring the same activity in the presence of a compound which is known to modulate MEK 1 or MEK 2 activity; and
(4) Method for obtaining useful data for the diagnosis and/or prognosis of peritoneal fibrosis, by determining the expression of MEK 1 and/or MEK 2 in a sample taken from a mammal and the comparing these MEK 1 and/or MEK 2 expression values with those in a healthy or ill mammal
The role of glycolysis in tumorigenesis: From biological aspects to therapeutic opportunities
No full textGlycolytic metabolism generates energy and intermediates for biomass production. Tumor-associated glycolysis is upregulated compared to normal tissues in response to tumor cell-autonomous or non-autonomous stimuli. The consequences of this upregulation are twofold. First, the metabolic effects of glycolysis become predominant over those mediated by oxidative metabolism. Second, overexpressed components of the glycolytic pathway (i.e. enzymes or metabolites) acquire new functions unrelated to their metabolic effects and which are referred to as “moonlighting” functions. These functions include induction of mutations and other tumor-initiating events, effects on cancer stem cells, induction of increased expression and/or activity of oncoproteins, epigenetic and transcriptional modifications, bypassing of senescence and induction of proliferation, promotion of DNA damage repair and prevention of DNA damage, antiapoptotic effects, inhibition of drug influx or increase of drug efflux. Upregulated metabolic functions and acquisition of new, non-metabolic functions lead to biological effects that support tumorigenesis: promotion of tumor initiation, stimulation of tumor cell proliferation and primary tumor growth, induction of epithelial-mesenchymal transition, autophagy and metastasis, immunosuppressive effects, induction of drug resistance and effects on tumor accessory cells. These effects have negative consequences on the prognosis of tumor patients. On these grounds, it does not come to surprise that tumor-associated glycolysis has become a target of interest in antitumor drug discovery. So far, however, clinical results with glycolysis inhibitors have fallen short of expectations. In this review we propose approaches that may allow to bypass some of the difficulties that have been encountered so far with the therapeutic use of glycolysis inhibitors
In vitro activity of propyl gallate-azole drug combination against fluconazole- and itraconazole-resistant Candida albicans strains
No full textAims: The influence of an antioxidant, propyl gallate (PG), on the In vitro antifungal activity of itraconazole and fluconazole, was investigated to determine whether PG could increase the antifungal activity and reduce strain resistance. Methods and Results: Susceptibility tests were performed against azole-resistant isolates of Candida albicans by the microbroth dilution method in the presence of PG at 400 mug ml(-1). PG-triazole combination brought about a marked reduction of inhibitory azole concentration. In particular, the MIC90 for itraconazole and fluconazole dropped from 1 mug ml(-1) to 0.125 mug ml(-1) and from >64 mug ml(-1)-8 mug ml(-1), respectively. Conclusions: It is likely that more than one mechanism is involved in the above synergistic interaction, including effects of PG on ATP synthesis, thus reducing the ABC transporters activity, or an effect on the target of azole, i.e. the P-450 cytochrome. Significance and Impact of the Study: The PG-triazole combination may have a role in future topical antifungal strategies but other studies are warranted
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