TIG3 Tumor Suppressor-Dependent Organelle Redistribution and Apoptosis in Skin Cancer Cells

TIG3 is a tumor suppressor protein that limits keratinocyte survival during normal differentiation. It is also important in cancer, as TIG3 level is reduced in tumors and in skin cancer cell lines, suggesting that loss of expression may be required for cancer cell survival. An important goal is identifying how TIG3 limits cell survival. In the present study we show that TIG3 expression in epidermal squamous cell carcinoma SCC-13 cells reduces cell proliferation and promotes morphological and biochemical apoptosis. To identify the mechanism that drives these changes, we demonstrate that TIG3 localizes near the centrosome and that pericentrosomal accumulation of TIG3 alters microtubule and microfilament organization and organelle distribution. Organelle accumulation at the centrosome is a hallmark of apoptosis and we demonstrate that TIG3 promotes pericentrosomal organelle accumulation. These changes are associated with reduced cyclin D1, cyclin E and cyclin A, and increased p21 level. In addition, Bax level is increased and Bcl-XL level is reduced, and cleavage of procaspase 3, procaspase 9 and PARP is enhanced. We propose that pericentrosomal localization of TIG3 is a key event that results in microtubule and microfilament redistribution and pericentrosomal organelle clustering and that leads to cancer cell apoptosis

Participation in medical decision-making across Europe: an international longitudinal multicenter study

Background: The purpose of this paper was to examine national differences in the desire to participate in decision-making of people with severe mental illness in six European countries. Methods: The data was taken from a European longitudinal observational study (CEDAR; ISRCTN75841675). A sample of 514 patients with severe mental illness from the study centers in Ulm, Germany, London, England, Naples, Italy, Debrecen, Hungary, Aalborg, Denmark and Zurich, Switzerland were assessed as to desire to participate in medical decision-making. Associations between desire for participation in decision-making and center location were analyzed with generalized estimating equations. Results: We found large cross-national differences in patients’ desire to participate in decision-making, with the center explaining 40% of total variance in the desire for participation (p<0.001). Averaged over time and independent of patient characteristics, London (mean=2.27), Ulm (mean=2.13) and Zurich (mean=2.14) showed significantly higher scores in desire for participation, followed by Aalborg (mean=1.97), where scores were in turn significantly higher than in Debrecen (mean=1.56). The lowest scores were reported in Naples (mean=1.14). Over time, desire for participation in decision-making increased significantly in Zurich (b=0.23) and decreased in Naples (b=-0.14). In all other centers, values remained stable. Conclusions: This study demonstrates that patients’ desire for participation in decisionmaking varies by location. We suggest that more research attention be focused on identifying specific cultural and social factors in each country to further explain observed differences across Europe

The role of ascorbate in antioxidant protection of biomembranes: Interaction with vitamin E and coenzyme Q

One of the vital roles of ascorbic acid (vitamin C) is to act as an antioxidant to protect cellular components from free radical damage. Ascorbic acid has been shown to scavenge free radicals directly in the aqueous phases of cells and the circulatory system. Ascorbic acid has also been proven to protect membrane and other hydrophobic compartments from such damage by regenerating the antioxidant form of vitamin E. In addition, reduced coenzyme Q, also a resident of hydrophobic compartments, interacts with vitamin E to regenerate its antioxidant form. The mechanism of vitamin C antioxidant function, the myriad of pathologies resulting from its clinical deficiency, and the many health benefits it provides, are reviewed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44796/1/10863_2004_Article_BF00762775.pd

Optimization, kinetic, and scaling-up of solvent-free lipase-catalyzed synthesis of ethylene glycol oleate emollient ester

The use of enzymatic catalysts is an alternative to chemical catalysts as they can help to obtain products with less environmental impact, considered sustainable within the concept of green chemistry. The optimization, kinetic, lipase reuse, and scale-up of enzymatic production of ethylene glycol oleate in the batch mode were carried out using the NS 88011 lipase in a solvent-free system. For the optimization step, a 23 Central Composite Design was used and the optimized condition for the ethylene glycol oleate production, with conversions above 99%, was at 70&nbsp;°C, 600&nbsp;rpm, substrates molar ratio of 1:2, 1&nbsp;wt% of NS 88011 in 32&nbsp;H of reaction. Kinetic tests were also carried out with different amounts of enzyme, and it showed that by decreasing the amount of the enzyme, the conversion also decreases. The lipase reuse showed good conversions until the second cycle of use, after which it had a progressive reduction reaching 83% in the fourth cycle of use. The scale-up (ninefold increase) showed promising results, with conversion above 99%, achieving conversions similar to small-scale reactions. Therefore, this work proposed an environmentally safe route to produce an emollient ester using a low-cost biocatalyst in a solvent-free system

Keratinocyte survival, differentiation, and death: many roads lead to mitogen-activated protein kinase

The epidermis is a dynamic and continually renewing surface that provides and maintains a life-sustaining interface with the environment. The epidermal keratinocyte, the major cell type of the epidermis, undergoes a complex and carefully choreographed program of differentiation. This process requires a balance between keratinocyte proliferation, differentiation, and apoptosis. This overview will concentrate on cascades that regulate the balance between keratinocyte cell proliferation and survival, and apoptosis and cell differentiation, with a particular emphasis on the role of the mitogen-activated protein kinase cascades. A summary of the literature suggests that extracellular regulated kinases function to promote keratinocyte proliferation and survival, whereas p38 mitogen-activated protein kinase functions to promote differentiation and apoptosis

Keratinocyte survival, differentiation, and death: many roads lead to mitogen-activated protein kinase

The epidermis is a dynamic and continually renewing surface that provides and maintains a life-sustaining interface with the environment. The epidermal keratinocyte, the major cell type of the epidermis, undergoes a complex and carefully choreographed program of differentiation. This process requires a balance between keratinocyte proliferation, differentiation, and apoptosis. This overview will concentrate on cascades that regulate the balance between keratinocyte cell proliferation and survival, and apoptosis and cell differentiation, with a particular emphasis on the role of the mitogen-activated protein kinase cascades. A summary of the literature suggests that extracellular regulated kinases function to promote keratinocyte proliferation and survival, whereas p38 mitogen-activated protein kinase functions to promote differentiation and apoptosis