Understanding autophagy in cell death control.

Autophagy is an evolutionarily conserved degradation pathway which primary functions as a cell survival adaptive mechanism during stress conditions. Autophagy is a tumor suppressor process and induction of the autophagic machinery can cause cell demise in apoptosis-resistant cancer. Thus, this metabolic pathway can act either to prevent or to promote carcinogenesis, as well as to modulate the response to anticancer therapies, included drug-induced apoptosis.

Modulation of programmed forms of cell death by intracoronary levosimendan during regional myocardial ischemia in anesthetized pigs.

Purpose: Powerful mediators of programmed cell death, such as apoptosis and autophagy, can contribute to myocyte cell loss during pathological cardiac conditions. Levosimendan has been shown to exert beneficial hemodynamic effects in presence of global myocardial ischemia and heart failure through vasodilatation and increase of cardiac contractility. Recently, the intracoronary administration of a bolus levosimendan was found to exert favourable cardiac anti-stunning effects without lowering arterial pressure, which limits the use of levosimendan mainly in coronary artery disease.

Protective activity of Theobroma cacao L. phenolic extract on AML12 and MLP29 liver cells by preventing apoptosis and inducing autophagy.

Theobroma cacao L. is known to have potential cardiovascular and cancer chemopreventive activities because of its high content of phenolic phytochemicals and their antioxidant capacities. In this work, we show for the first time that cocoa inhibits drug-triggered liver cytotoxicity by inducing autophagy.

mTOR, S6 and AKT expression in relation to proliferation and apoptosis/autophagy in glioma.

Background: The mammalian target of rapamycin (mTOR) controls cell growth through protein synthesis regulation. It can be activated by protein kinase B (AKT) or through ribosomal S6 kinase (S6K1). In malignant glioma, mTOR inhibitors have antiproliferative and proapoptotic effects and mTOR has been suggested as a target of therapies, thus it is worthwhile to verify its relations with the phosphatidylinositol-3-kinase (PI3)/AKT cascade, proliferation and apoptosis in human gliomas.

Down-regulation of the HGF/MET autocrine loop induced by celecoxib and mediated by P-gp in MDR-positive human hepatocellular carcinoma cell line.

Many tumors are resistant to drug-induced cell-cycle arrest and apoptosis. We have reported that apoptosis can be restored in human multidrug-resistant (MDR) hepatocellular carcinoma cell lines by celecoxib. Here we show that P-glycoprotein (P-gp) mediates cell-cycle arrest and autophagy induced by celecoxib in human MDR overexpressing hepatocellular carcinoma cell line by down-regulation of the HGF/MET autocrine loop and Bcl-2 expression.

Autophagy inhibition enhances anthocyanin-induced apoptosis in hepatocellular carcinoma.

Anthocyanins extracted from the berries of Phillyrea latifolia L., Pistacia lentiscus L., and Rubia peregrina L.

Sequence uniqueness and sequence variability as modulating factors of human anti-HCV humoral immune response.

We recently compared the HCV polyprotein to the human proteome in order to test whether amino acid sequences unique to the virus could represent immunodominant epitopic determinants of the human humoral immune response against HCV. We identified a relatively limited number of HCV fragments with no/low similarity to the human host that represented exclusive HCV motifs. In this study, the peptides corresponding to low/zero similarity sequences were synthesized and assayed with HCV-infected sera.

Stat3 expression and its correlation with proliferation and apoptosis/autophagy in gliomas.

Signal transducer and activator of transcription-3 (Stat3) was studied along with several steps of the PI3/Akt pathway in a series of 64 gliomas that included both malignant and low-grade tumors, using quantitative immunohistochemistry, Western blotting, and molecular biology techniques. The goal of the study was to investigate whether activated Stat3 (phospho-Stat3) levels correlated with cell proliferation, apoptosis, and autophagy. Stat3 and activated Akt (phospho-Akt) expression increased with malignancy grade, but did not correlate with proliferation and survival within the category of glioblastomas.

P-glycoprotein mediates celecoxib-induced apoptosis in multiple drug-resistant cell lines.

In several neoplastic diseases, including hepatocellular carcinoma, the expression of P-glycoprotein and cyclooxygenase-2 (COX-2) are often increased and involved in drug resistance and poor prognosis. P-glycoprotein, in addition to drug resistance, blocks cytochrome c release, preventing apoptosis in tumor cells. Because COX-2 induces P-glycoprotein expression, we evaluated the effect of celecoxib, a specific inhibitor of COX-2 activity, on P-glycoprotein-mediated resistance to apoptosis in cell lines expressing multidrug resistant (MDR) phenotype.

Mucin-depleted foci are modulated by dietary treatments and show deregulation of proliferative activity in carcinogen-treated rodents.

The correlation between mucin-depleted foci (MDF) and colon carcinogenesis was studied in F344 rats initiated with 1,2-dimethylhydrazine and treated with a chemopreventive regimen (polyethylene glycol, PEG) or with a promoting diet (high-corn oil). High corn oil diet increased MDF, while PEG reduced them. The expression of p27 and p16, inhibitors of cyclin-dependent kinases, which inhibit the progression of the cell cycle, was studied by immunohistochemistry in MDF and in aberrant crypt foci (ACF) of control rats.

Proteomic definition of a desmoglein linear determinant common to Pemphigus vulgaris and Pemphigus foliaceous.

Background: A number of autoimmune diseases have been clinically and pathologically characterized. In contrast, target antigens have been identified only in a few cases and, in these few cases, the knowledge of the exact epitopic antigenic sequence is still lacking. Thus the major objective of current work in the autoimmunity field is the identification of the epitopic sequences that are related to autoimmune reactions.

Inactivation of PEMT2 in hepatocytes initiated by DENA in fasted/refed rats.

Phosphatidylethanolamine N-methyltransferase (PEMT) is the enzyme that converts phosphatidylethanolamine (PE) into phosphatidylcholine. We have previously shown that PEMT suppressed hepatoma growth by triggering apoptosis. We investigate whether PEMT controlled cell death and cell proliferation triggered by fasting/refeeding and whether it is a marker of early preneoplastic lesions.

Gene therapy in cancer: the missing point.

Over the last century cancer research has produced data leading to a composite picture where gene mutations and epigenetic phenomena strictly relate and overlap. This complexity has repercussions on the anti-cancer therapeutical strategies. The therapeutic pathway paved by the kochian one-cause/one disease principle fails in front of a multigenic multiphenomena disease like cancer.

Resveratrol inhibits cell cycle progression in U937 cells.

Resveratrol, a naturally occurring stylbene present in grapes, is proposed to be responsible for the positive effects of red wine consumption on cardiovascular diseases (French paradox). In recent years this molecule has also been proposed as a cancer chemopreventive agent. The aim of the present study was to investigate the mechanisms by which resveratrol inhibits tumor growth.

Sepsis induces DNA fragmentation in rat skeletal muscle.

Recent studies have demonstrated the activation of skeletal muscle DNA fragmentation in some catabolic conditions. In an attempt to elucidate if sepsis (a catabolic state) was also associated with muscle apoptosis, sepsis was induced by cecal ligation and puncture, and the results clearly show an induction of DNA fragmentation in gastrocnemius muscle following the induction of the septic state. Administration of rolipram (an inhibitor of tumour necrosis factor-a (TNF-alpha) synthesis) to septic rats clearly prevented the increased DNA fragmentation, suggesting that TNF-alpha is involved in the activation of the apoptotic events in septic rat skeletal muscle.

Expression of phosphatidylethanolamine N-methyltransferase in human hepatocellular carcinomas.

Objective: Hepatic phosphatidylethanolamine is converted into phosphatidylcholine by the enzyme phosphatidylethanolamine N-methyltransferase (PEMT) when the dietary choline supply is inadequate. Our previous reports implicated PEMT in the regulation of hepatocyte growth and transformation. In the present study, we analyzed PEMT activity, PEMPT gene status and its mRNA expression in 29 human hepatocellular carcinomas (HCC).

Enhanced growth of colorectal aberrant crypt foci in fasted/refed rats involves changes in TGFbeta1 and p21CIP expressions.

We previously demonstrated that fasting/refeeding enhances the initiation phase of liver and colorectal carcinogenesis in rats. The present study was undertaken to establish whether cycles of fasting/refeeding carried out during the promotion phase of carcinogenesis may also affect the formation of aberrant crypt foci (ACF), preneoplastic lesions induced in the colon by azoxymethane (AOM). We were also interested in studying whether this effect might be mediated by changes in the proliferation, apoptosis or expression of TGFbeta1 and p21CIP genes in the colon.