Targeted inhibition of Livin resensitizes renal cancer cells towards apoptosis

Cancer cells are typically characterized by apoptosis deficiency. In order to investigate a possible role for the anti-apoptotic livin gene in renal cell cancer (RCC), we analyzed its expression in tumor tissue samples and in RCC-derived cell lines. In addition, we studied the contribution of livin to the apoptotic resistance of RCC cells by RNA interference (RNAi). Livin gene expression was detected in a significant portion of RCC tumor tissue specimens (13/14, 92.9%) and tumor-derived cell lines (12/15, 80.0%). Moreover, targeted inhibition of livin by RNAi markedly sensitized RCC cells towards proapoptotic stimuli, such as UV irradiation or the chemotherapeutic drugs etoposide, 5-fluorouracil, and vinblastine. These effects were specific for livin expressing tumor cells. We conclude that livin can contribute significantly to the apoptosis resistance of RCC cells. Targeted inhibition of livin could represent a novel therapeutic strategy to increase the sensitivity of renal cancers towards pro-apoptotic agents. Received 30 November 2006; received after revision 22 February 2007; accepted 20 March 2007     

Der Einfluß der Nebenniere auf die Kreislaufwirkung des Adrenalins

Summary Traces of nor-adrenaline restore the vascular action of adrenaline altered in epinephrectomized dogs to the reaction of the normal animal. Therefore it is claimed that the adrenals discharge one or several substances into the blood stream, which are necessary for the usual peripheral vascular action of adrenaline. Further investigations are in progress.     

Mutations in LMF1 cause combined lipase deficiency and severe hypertriglyceridemia

Hypertriglyceridemia is a hallmark of many disorders, including metabolic syndrome, diabetes, atherosclerosis and obesity. A well-known cause is the deficiency of lipoprotein lipase (LPL), a key enzyme in plasma triglyceride hydrolysis. Mice carrying the combined lipase deficiency (cld) mutation show severe hypertriglyceridemia owing to a decrease in the activity of LPL and a related enzyme, hepatic lipase (HL), caused by impaired maturation of nascent LPL and hepatic lipase polypeptides in the endoplasmic reticulum (ER). Here we identify the gene containing the cld mutation as Tmem112 and rename it Lmf1 (Lipase maturation factor 1). Lmf1 encodes a transmembrane protein with an evolutionarily conserved domain of unknown function that localizes to the ER. A human subject homozygous for a deleterious mutation in LMF1 also shows combined lipase deficiency with concomitant hypertriglyceridemia and associated disorders. Thus, through its profound effect on lipase activity, LMF1 emerges as an important candidate gene in hypertriglyceridemia.     

Common Molecular Mechanisms of Mammary Gland Development and Breast Cancer

During its lifetime, the mammary gland undergoes many phases of development and differentiation. Much of this occurs during puberty, when the ductal epithelium expands by branching morphogenesis, invading the surrounding fat pad to form an organised mammary tree. Throughout its existence, the epithelium will go through several cycles of proliferation and cell death during pregnancy, lactation and involution. Many of the signalling mechanisms which control the initial invasion of the fat pad by the epithelium, and regulate its continuing plasticity, can be harnessed or corrupted by tumour cells in order to support their aberrant growth and progression towards invasion. This is true not just for the epithelial cells themselves but also for cells in the surrounding microenvironment, including fibroblasts, macrophages and adipocytes. This review examines the complex web of signalling and adhesion interactions controlling branching morphogenesis, and how their alteration can promote malignancy. Current in vivo and in vitro mammary gland models are also discussed. (Part of a Multi-author Review)     

Nanostructured Functional Thermoplastic Polymeric Materials Based on the Molecular Control of the Blending

1 Results The development of the concepts of nanotechnology has given an important impact on the design of new polymer based materials which are in most cases characterized by a multiphase morphology. When at least one phase has nanometric dimension(s) the system can be considered as a nanocomposite where the interface is not only determining for the adhesion but also may play a role in some bulk properties. Indeed in nanostructured multiphase solids the interface is significant as a bulk component. The...     

The Three-component One-pot Synthesis of 4,6-Diarylpyrimidin-2(1h)-ones and 9-Phenyl-8-oxa-10,12-diaza-tricyclo[7.3.1.0~(2,7)]trideca-2(7),3,5-trien-11-one

1 Results Pyrimidinones (PMs) are a class of important heterocycles which have been well documented throughout the literature due to their biological importance. They exhibit a wide range of pharmaceutical and therapeutic properties[1].A rapid and efficient one-pot method for the synthesis of 4,6-diarylpyrimidin-2(1H)- ones and related heterocycles is described.The condensation of acetophenone derivatives,aldehydes and urea in the presence of sulfamic acid was employed to synthesize a variety of pyrimid...     

Notizie preliminari sull'azione fitodinamica dell'acido difenililacetico sulla pianta del tabacco

Summary The application of diphenylilacetic acid has shown favorable effects on the growth of tobacco plants. Solutions containing 10 p.p.m. and 20 p.p.m. produce, in weight, an almost double growth in treated plants in comparison with the controls. Diphenylilacetic acid can be considered as a growth-promoting substance. The data are not definite.     

Heterostructure in ZnO Nano-Tetrapods

1 Introduction 　　Nanoscale science and technology have attracted greatattention since the novel properties become dominant for well-known materials as their sizes reduced to some critical dimension. These properties frequently originate in lattice distortions, structure transformations etc[1]. The variations of size and structure ofnanocrystals lead to the change of their electronic structures. Very recently, nanoscale materials with different electronic structures were utilized in fabricating nanoscale junctions[2]. 　　……     

Forecast accuracy after pretesting with an application to the stock market

In econometrics, as a rule, the same data set is used to select the model and, conditional on the selected model, to forecast. However, one typically reports the properties of the (conditional) forecast, ignoring the fact that its properties are affected by the model selection (pretesting). This is wrong, and in this paper we show that the error can be substantial. We obtain explicit expressions for this error. To illustrate the theory we consider a regression approach to stock market forecasting, and show that the standard predictions ignoring pretesting are much less robust than naive econometrics might suggest. We also propose a forecast procedure based on the ‘neutral Laplace estimator’, which leads to an improvement over standard model selection procedures. Copyright © 2004 John Wiley & Sons, Ltd.