Invasion and metastasis are the hallmarks of malignant tumor progression and the main cause of death in cancer. The embryonic program ''epithelial-mesenchymal transition'' (EMT) is thought to trigger invasion by allowing tumor cell dissemination. Here, we describe that the EMT-inducing transcriptional repressor ZEB1 promotes colorectal cancer cell metastasis and loss of cell polarity. Thereby, ZEB1 suppresses the expression of cell polarity factors, in particular of Lgl2, which we found reduced in colorectal and breast cancers. We further show that retention of Lgl2 expression is critical for the epithelial phenotype and that its loss might be involved in metastasis. Thus, by linking EMT, loss of polarity, and metastasis, ZEB1 is a crucial promoter of malignant tumor progression. [Cancer Res 2008;68(2):537-44]

Genetic analysis of the M2 sequence of European porcine influenza A viruses reveals a high prevalence of amantadine resistance due to the substitution of serine 31 by asparagine in all three circulating subtypes, H1N1, H3N2 and H1N2. The M segment of all resistant strains belongs to a single genetic lineage. Whereas the first amantadine-resistant porcine strain was isolated in 1989, isolation of the last amantadine-susceptible strain dates to 1987, suggesting a displacement of amantadine-susceptible viruses by resistant strains soon after emergence of the mutation. Analysis of natural selection by codon-based tests indicates negative selection of codons 30, 31 and 34 which confer amantadine resistance. The codons 2, 11–28 and 54 of porcine and human strains exhibit differences in the patterns of substitution rates, suggesting different selection modes. Transfer of amantadine resistance by exchange of the M segment and viability of recombinant A/WSN/33 viruses with avian-like M segments raises concerns about the emergence of natural human reassortants.

The application of microwave technology to a diverse range of materials and processes has resulted in a wide spectrum of materials that are commercially processed using microwaves, from the heating of food to the vulcanisation of rubber to the sintering of specialty ceramics. Microwave sintering of elemental or alloy metal powders has gained significance in recent times as a novel processing method since it offers many advantages over the conventional sintering method. Despite substantial R&D investment in this area in the past two decades, no competitive microwave technology has yet emerged for powder metallurgy (PM) sintering. In sharp contrast, because it is 'obvious' that microwaves are reflected by metals, it is not uncommon to be unable to locate many journal papers or literature, wherein metal powders have been sintered in a microwave field. This paper reports the improved mechanical properties and microstructural development of microwave sintered copper and nickel steel PM parts as compared with that obtained using conventional sintering technique.The paper describes the fabrication details of the FC-0208 and FN-0208 composition steel PM parts, and the in house modified commercial microwave oven used for sintering. Microwave sintering resulted in higher sintered density and improved mechanical properties for both Cu and Ni steel PM parts as compared with that processed using conventional sintering under identical conditions. The improved mechanical properties can be attributed primarily to more uniform distribution of the alloying elements, which resulted in greater material homogeneity at the nano-and microlevels as revealed by the Cu and Fe X-ray maps using high spatial resolution scanning transmission electron microscopy (STEM). The optical micrographs of both the etched and unetched samples clearly showed development of novel sintered microstructures having distinct characteristics for the porosity distributions: smooth and rounded pores with low stress concentration regions for microwave sintering as against sharp, triangular and wedge shaped pores with high stress concentration regions for conventional sintering.

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Transendothelial migration is a key step in the extravasation of tumor cells during metastasis formation. Here, we have classified 45 human tumor cell lines derived from various tissues according to their capacity for transendothelial migration in vitro. We could distinguish cell lines showing strong transmigration (TEMþ cell lines) from others that did not transmigrate (TEM2 cell lines). By DNA microarray analysis we could cluster TEMþ and TEM2 cell lines according to their gene expression pattern and identify genes differentially expressed between the 2 groups. Among these we found the integrin b3 subunit to be highly expressed in TEMþ cell lines as compared to TEM2 cell lines. Cell surface localization of avb3 integrin receptors was exclusively found in TEMþ cell lines. Transendothelial migration of TEMþ cells but not their adhesion to the endothelial cells, or invasion into collagen gels could be blocked with an antibody against avb3 integrin and by RNAi mediated knock-down of the integrin b3 subunit. These data establishes avb3 integrin as one key component of the transendothelial migration process of tumor cells, and as a potential target for anti-metastatic therapy. Our gene expression analysis of a defined collection of tumor cell lines can be used as a starting point to identify further genes functionally involved in transendothelial migration. ' 2007 Wiley-Liss, Inc.Key words: avb3 integrin; metastasis formation; transendothelial migration Metastasis formation is a complex process, which involves the detachment of invasive cells from the tumor mass, their penetration into the surrounding stroma and blood or lymph vessels and finally their extravasation into the target organs. The metastatic cascade requires dynamic alterations of the interactions among the tumor cells and of tumor cells with other cell types or components of the extracellular matrix. In line with this, several cell surface adhesion receptors such as cadherins and integrins have been identified that act as either negative or positive factors of tumor invasion and metastasis. [1][2][3][4] Matrix adhesion mediated by integrins was shown to be essential for tumor cell migration in stromal tissues, and inhibition of this interaction using blocking antibodies or interfering peptides reduces metastasis formation in animal models. 3 Integrins also mediate interaction of tumor cells with platelets and leukocytes, which increases resistance to shear stress in the vasculature. 4 One key step of metastasis is the extravasation of tumor cells across the endothelium. This process requires the adhesion of tumor cells to endothelial cells and their transmigration across the endothelial border into the stroma of the target organ. Although transendothelial migration is of considerable interest both from a cell and tumor biological perspective its underlying molecular mechanisms are rather ill defined. Molecular determinants have been mainly identified by candidate approaches based on analogies drawn from studies on the transendothelial migration of leu...