Breast cancer is the most prominent cancer among females in the United States. There are a number of risk factors associated with development of breast cancer, including consumption of a high-fat diet and obesity. Plasminogen activator inhibitor-1 (PAI-1) is a cytokine upregulated in obesity whose expression is correlated with a poor prognosis in breast cancer. As a key mediator of adipogenesis and regulator of adipokine production, peroxisome proliferator-activated receptor-γ (PPAR-γ) is involved in PAI-1 expression from adipose tissue. We summarize the current knowledge linking PPAR-γ and PAI-1 expression to high-fat diet and obesity in the risk of breast cancer.

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Recent reports have indicated that Trivalent Actinide-Lanthanide Separation by Phosphorus reagent Extraction from Aqueous Komplexes (TALSPEAK)-type separations chemistry can be improved through the replacement of bis-2-ethyl(hexyl) phosphoric acid (HDEHP) and diethylenetriamine-N,N,N 0 ,N 00 ,N 00 -pentaacetic acid (DTPA) with the weaker reagents 2-ethyl(hexyl) phosphonic acid mono-2-ethylhexyl ester (HEH [EHP]) and N-(2-hydroxyethyl) ethylenediamine-N,N 0 ,N 0 -triacetic acid (HEDTA), respectively. This modified TALSPEAK has been provided with an adjusted acronym of TALSQuEAK (Trivalent Actinide-Lanthanide Separation using Quicker Extractants and Aqueous Komplexes). Among several benefits, TALSQuEAK chemistry provides more rapid phase transfer kinetics, is less reliant on carboxylic acids to mediate lanthanide extraction, and allows a simplified thermodynamic description of the separations process that generally requires only parameters available in the literature to describe metal transfer. This article focuses on the role of carboxylic acids in aqueous ternary (M-HEDTA-carboxylate) complexes, americium/lanthanide separations, and extraction kinetics. Spectrophotometry (UV-Vis) of the Nd 3þ hypersensitive band indicates the presence of aqueous ternary Nd-Lac-HEDTA species (Lac ¼ lactate, K 111 ¼ 1.83 AE 0.01 at 1.0 mol L À1 ionic strength, Nd(HEDTA) þ Lac À À! À Nd(HEDTA)Lac À ). While lower levels (0.1 mol L À1 vs. 1.0 mol L À1 ) of carboxylic acid will still be necessary to control pH and encourage phase transfer of the heavier lanthanides, application of different carboxylic acids does not have an overwhelming impact on Ln/Am separations or extraction kinetics relative to conventional TALSPEAK separations. TALSQuEAK separations come to equilibrium in two to five minutes depending on the system pH using only 0.1 mol L À1 total lactate or citrate.

Objectives-Increased levels of urokinase-type plasminogen activator (uPA) are associated with shortened overall survival in ovarian cancer patients. Additionally, elevated levels of the serine protease inhibitor (serpin), plasminogen activator inhibitor-1 (PAI-1), a uPA inhibitor, have also been correlated with an unfavorable prognosis in ovarian cancer. Therefore, it is critical to understand the signaling pathways that regulate PAI-1 and uPA expression in cancer cell migration-invasion.Methods-We studied the PI3K/Akt, Rho kinase/ROCK, p38 MAPK and MEK pathways and their modulation of PAI-1 and uPA expression and wound-induced cell migration in SKOV-3 ovarian cancer cells. The PI3K/Akt pathway was further examined using pharmacological inhibitors (LY294002 and wortmannin), Akt siRNA, constitutively active Akt adenovirus and treatment with IGF-1/insulin in the SKOV-3 cells.Results-The PI3K/Akt pathway negatively regulates PAI-1 expression and positively correlates with migratory abilities and uPA expression in SKOV-3 cells. A reduction in active Akt results in an increase in PAI-1 expression coupled with a decrease in uPA expression to ultimately result in reduced cell migration and invasion. By contrast, an increase in Akt activity reduces PAI-1 expression and results in an increase in SKOV-3 wound-induced cell migration. Furthermore, IGF-1 and insulin stimulated SKOV-3 migration by altering the balance between uPA and PAI-1 to favor uPA, and the enhanced migration was attenuated by treatment with LY294002 indicating PI3K/Akt in this pathway. Conclusions-These results suggest an overall ovarian tumor-protective role for PAI-1, and that the PI3K/Akt signaling pathway regulates the ratio of PAI-1:uPA to either increase or decrease cell migration.

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We have previously mapped a liver tumor suppressor locus to human chromosome 11p11.2-p12 using a functional model of tumor suppression. Using this model system, we have employed a candidate gene approach to identify potential liver tumor suppressor genes. Thirty-eight known genes have been positioned in human 11p11.2-p12 by the Human Genome Project. Here we show that four of these genes (guanine nucleotide binding protein gamma 3; mitochondrial carrier homolog 2; p53-induced protein (PIG11), and pRDI-BF1-rIZ1 domain containing 11) localized to the minimal liver tumor suppressor region within 11p11.2-p12. In fact, all of these genes mapped to human 11p11.2, allowing refinement of the liver tumor suppressor region to this cytogenetic band. Three of the four genes (mitochondrial carrier homolog 2, PIG11, and pRDI-BF1-rIZ1 domain containing 11) were uniformly expressed by an index panel of suppressed microcell hybrid cell lines, identifying them as candidate liver tumor suppressor genes. In a preliminary analysis of four human hepatocellular carcinoma cell lines (HepG2, Hep3B, SNU398, and SNU449), the transcript for PIG11 was lost or significantly decreased in two of these cell lines (HepG2 and Hep3B), suggesting the potential involvement of PIG11 in some human hepatocellular carcinomas. The results of this study extended our previous knowledge of genes located in the minimal liver tumor suppressor region of human 11p11.2 and identified several candidate liver tumor suppressor genes from this region. Further characterization of these candidates will provide new insight into the role of human 11p11.2 in the molecular pathogenesis of human liver cancer.