Shaping picosecond ellipsoidal laser pulses with periodic intensity modulation for electron photoinjectors.

A method for shaping periodic intensity distributions of strongly chirped picosecond laser pulses in the infrared range by periodic phase modulation of the spectrum is proposed. The dependence of the time modulation period and depth on the parameters of periodic phase modulation of the spectrum is analyzed by analytical and numerical methods. It is demonstrated that the intensity distribution structure obtained at second- and fourth-harmonic generation can be retained by introducing an angular chirp. The electron bunch dynamics at the photoinjector test facility at DESY in Zeuthen (PITZ) was modeled numerically using ellipsoidal laser pulses with intensity modulation.

beta-catenin signaling pathway and the tolerance of breast cancer cells to hypoxic conditions.

We have previously shown that Snail, a regulator of epithelial-mesenchymal transition, is activated in the hypoxia-resistant breast cancer cell line HBL100. The purpose of this study was to evaluate the role of beta-catenin signaling pathway in the maintenance of breast cancer cells 'tolerance to hypoxia. The breast cancer cell lines MCF-7 and HBL-100 were used in this study; HBL-100 cells were characterized by increased resistance to hypoxia. We have demonstrated that the transcription factor beta-catenin is activated in hypoxic conditions and the beta-catenin activity is supported by Snail, a regulator of epithelial-mesenchymal transition. The activated beta-catenin regulates the expression of genes of the cell response to hypoxia and thus, it maintains the growth of breast cancer in the reduced oxygen conditions. The coordinated activation of Snail/beta-catenin/HIF-1alpha proteins in cell may be considered as an important factor of tumor resistance to hypoxia.

Phosphorylated Akt1 in human breast cancer measured by direct sandwich enzyme-linked immunosorbent assay: Correlation with clinicopathological features and tumor VEGF-signaling system component levels.

Protein kinase B (Akt) plays a major role in the regulation of breast cancer growth, survival, hormone, drug and radiosensitivity, but the clinical value of its expression and activation in human tumors is unclear. Activated Akt1 (pAkt1) expression was quantified in a series of 46 breast cancer and adjacent mammary gland samples by a direct Path-Scan PhosphoAkt1 (Ser473) sandwich ELISA kit. VEGF, sVEGFR1 and sVEGFR2 levels were measured simultaneously by standard ELISA kits. Forty-nine percent of the tumors had an increased pAkt1 level as compared to adjacent tissue. pAkt1 levels were significantly higher in stage IIb than in stage I-IIa tumors. The frequency of pAkt1 elevation was positively associated with tumor size and malignancy grade. pAkt1 was also twice as frequently increased in PgR-negative as in PgR-positive tumors, while its mean level was significantly higher in ER-positive than in ER-negative tumors. VEGF, sVEGFR1 and sVEGFR2 were increased in 73-85% of the tumors, but no associations with most clinicobiological factors and pAkt1 level were found. In conclusion, activation of Akt1 is not associated with VEGF signaling protein expression in breast cancer but is related to tumor size, grade of malignancy, and steroid receptor status.

Phosphatidylinositol-3 kinase dependent pathways: the role in control of cell growth, survival, and malignant transformation.

Phosphatidylinositol-3 kinase (PI3K) is one of the most important regulatory proteins that is involved in different signaling pathways and controlling of key functions of the cell. The double-enzymatic activity of PI3K (lipid kinase and protein kinase) as well as the ability of this enzyme to activate a number of signal proteins including some oncoproteins determines its fundamental significance in regulation of cell functions such as growth and survival, aging, and malignant transformation. Among the main effectors of PI3K are the mitogen-transducing signal proteins (protein kinase C, phosphoinositide-dependent kinases, small G-proteins, MAP (mitogen activated protein) kinases), which are activated either via their interaction with lipid products of PI3K or through PI3K-dependent phosphorylation of proteins. The anti-apoptotic effect of PI3K is realized by activation of proteins from another signaling pathway--protein kinase B (PKB) and/or PKB-dependent enzymes (GSK-3, ILK). PI3K plays a critical role in malignant transformation. PI3K itself possesses oncogenic activity and also forms complexes with some viral or cellular oncoproteins (src, ras, rac, alb, T-antigen), whose transforming activities are realized only in presence of PI3K. The transforming effect of PI3K is supposed to occur on the basis of complex alterations in cellular signaling pathways: appearance of constitutively generated PI3K-dependent mitogen signal and activation of some protooncogenes (src, ras, rac, etc.), PI3K/PKB-pathway stimulation resulting in delay of apoptosis and increase of cell survival, and actin cytoskeleton reorganization.