Troglitazone suppresses telomerase activity independently of PPARγ in estrogen-receptor negative breast cancer cells

<p>Abstract</p> <p>Background</p> <p>Breast cancer is one the highest causes of female cancer death worldwide. Many standard chemotherapeutic agents currently used to treat breast cancer are relatively non-specific and act on all rapidly dividing cells. In recent years, more specific targeted therapies have been introduced. It is known that telomerase is active in over 90% of breast cancer tumors but inactive in adjacent normal tissues. The prevalence of active telomerase in breast cancer patients makes telomerase an attractive therapeutic target. Recent evidence suggests that telomerase activity can be suppressed by peroxisome proliferator activated receptor gamma (PPARγ). However, its effect on telomerase regulation in breast cancer has not been investigated.</p> <p>Methods</p> <p>In this study, we investigated the effect of the PPARγ ligand, troglitazone, on telomerase activity in the MDA-MB-231 breast cancer cell line. Real time RT-PCR and telomerase activity assays were used to evaluate the effect of troglitazone. MDA-MB-231 cells had PPARγ expression silenced using shRNA interference.</p> <p>Results</p> <p>We demonstrated that troglitazone reduced the mRNA expression of hTERT and telomerase activity in the MDA-MB-231 breast cancer cell line. Troglitazone reduced telomerase activity even in the absence of PPARγ. In agreement with this result, we found no correlation between PPARγ and hTERT mRNA transcript levels in breast cancer patients. Statistical significance was determined using Pearson correlation and the paired Student's <it>t </it>test.</p> <p>Conclusions</p> <p>To our knowledge, this is the first time that the effect of troglitazone on telomerase activity in breast cancer cells has been investigated. Our data suggest that troglitazone may be used as an anti-telomerase agent; however, the mechanism underlying this inhibitory effect remains to be determined.</p

Pressure Profile Designing in Superplastic Forming Based on the Strain Rate and on Post-forming Properties

In this work, the feasibility of reducing the cycle time in superplastic forming through a selective approach in the algorithm that calculates the forming pressure profile was investigated. First, a 3D numerical model of the blow forming process is created. Then, the blank was partitioned in different characteristic areas according to their strain and strain rate histories. Thus, different pressure profiles were numerically calculated choosing different combinations of those partitions of the blank. Experimental trials were finally carried out in order to explore the potential reduction of the forming time that can be achieved through the described approach without affecting the post-forming properties of the formed specimens. Post-forming properties were measured in terms of thickness distribution, mean grain size, and cavitation effects along the formed sheet. In particular, experiments were performed both with the conventional approach (with the whole sheet being monitored) and considering only the area of the sheet that experiences the highest strain values at the end of the forming process. Results highlighted that this latter approach can efficiently reduce the cycle time

Adiponectin: a key playmaker adipocytokine in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and can progress to cirrhosis, liver failure, and hepatocellular carcinoma. In the last two decades, the prevalence of NAFLD has been growing in most developed countries, mainly as a consequence of its close association with obesity and diabetes mellitus. The exact pathogenesis of NAFLD and especially the mechanisms leading to disease progression have not been completely understood. Adipocytes produce and secrete several bioactive substances known as adipocytokines which are implicated in the pathogenesis of the disease. Among them, adiponectin is an insulin-sensitizing adipocytokine possessing multiple beneficial effects on obesity-related medical complication. This review focuses on the role of adiponectin in NAFLD pathogenesis and its potential use as a diagnostic tool but also as therapeutic target for NAFLD management