ABSTRACT
Ability to stimulate angiogenesis/lymphangiogenesis is recognized as an inherent feature of cancer cells providing necessary conditions for their growth and dissemination. "Angiogenic switch" is one of the earliest consequences of malignant transformation that encompasses a great number of genes and triggers a complex set of signaling cascades in endothelial cells. The processes of tumor microvasculature development are closely connected to the steps of carcinogenesis (from benign lesions to invasive forms) and occur through multiple deviations from the norm. Analysis of expression of proangiogenic factors at successive steps of cervical cancer development (intraepithelial neoplasia, cancer in situ, microinvasive, and invasive cancer) enables to reconstruct the regulatory mechanisms of (lymph-)angiogenesis and to discriminate the most important components. This review presents detailed analysis of literature data on expression of the key regulators of angiogenesis in cervical intraepithelial neoplasia and cervical cancer. Their possible involvement in molecular mechanisms of neoplastic transformation of epithelial cells, as well as invasion and tumor metastasis is discussed. Correlation between expression of proangiogenic molecular factors and various clinicopathological parameters is considered, the potential of their use in molecular diagnostics and targeted therapy of cervical cancer is reviewed. Particular attention is paid to relatively poorly studied regulators of lymphangiogenesis and "non-VEGF dependent", or alternative, angiogenic pathways that constitute the prospect of future research in the field.
Subject(s)
Adenocarcinoma in Situ/genetics , Carcinoma, Squamous Cell/genetics , Gene Expression Regulation, Neoplastic , Neovascularization, Pathologic/genetics , Uterine Cervical Dysplasia/genetics , Uterine Cervical Neoplasms/genetics , Adenocarcinoma in Situ/metabolism , Adenocarcinoma in Situ/pathology , Angiogenic Proteins/genetics , Angiogenic Proteins/metabolism , Carcinogenesis/genetics , Carcinogenesis/metabolism , Carcinogenesis/pathology , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , Disease Progression , Female , Humans , Intercellular Signaling Peptides and Proteins/genetics , Intercellular Signaling Peptides and Proteins/metabolism , Lymphangiogenesis/genetics , Neoplasm Invasiveness , Neovascularization, Pathologic/metabolism , Neovascularization, Pathologic/pathology , Signal Transduction , Uterine Cervical Neoplasms/metabolism , Uterine Cervical Neoplasms/pathology , Uterine Cervical Dysplasia/metabolism , Uterine Cervical Dysplasia/pathologyABSTRACT
Recent data on the biosynthesis of poly(3-hydroxybutyrate) (PHB) and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHB/V) and its regulation in bacteria are reviewed, with special emphasis on the properties and regulation of the relevant enzymes and their genes. Some conditions promoting the synthesis of PHB and PHB/V by natural, mutant, and recombinant producers are considered.
Subject(s)
Bacteria/metabolism , Polyesters/metabolismABSTRACT
Citrate synthase (citrate oxaloacetate-lyase, CoA-acetylating; EC 4.1.3.7, CS) was isolated and purified to homogeneity from a methylotrophic producer of polyhydroxybutyrate (PHB), Methylobacterium extorquens 15. The purification procedure includes streptomycin sulfate treatment of cell-free extract, ammonium sulfate fractionation, two steps of hydrophobic chromatography, and ion-exchange chromatography. The specific activity of the final enzyme preparation was 24 U/mg protein. The enzyme has apparent molecular weight 260 kD and consists of four 66-kD subunits. The enzyme shows a sigmoid saturation curve with CoASA (h = 1.3). Kinetic parameters are: K(m) = 84 microM for CoASA; K(m) = 12 microM for oxaloacetate; Vmax = 29.7 mumoles/min per mg protein. KCl at concentrations up to 80 mM activates the CS. ATP exerts a significant inhibitory effect on the enzyme activity, whereas NAD(P)H, isocitrate, alpha-ketoglutarate, ADP, acetoacetyl-CoA, glyoxylate, and glutamate have no influence. A possible role of the CS in coordinated control of CoASA transformation through the tricarboxylic acid cycle and PHB biosynthesis in this methylotroph is discussed.
Subject(s)
Citrate (si)-Synthase/isolation & purification , Gram-Negative Aerobic Bacteria/enzymology , Chromatography, Liquid , Citrate (si)-Synthase/metabolism , Electrophoresis, Polyacrylamide Gel , Hydrogen-Ion ConcentrationABSTRACT
The effect of ion plasma light flux on the genomes of auxotrophic Escherichia coli strain and Drosophilla melanogaster has been examined. Essentially no mutagenic effect was found in doses close to therapeutic ones.
Subject(s)
Mutagenesis/radiation effects , Animals , Drosophila melanogaster/genetics , Drosophila melanogaster/radiation effects , Escherichia coli/genetics , Escherichia coli/radiation effects , Female , Helium , Male , Microscopy, Phase-Contrast , MosaicismABSTRACT
The study of the genotoxic activity of ethidium bromide and bleomycin by the two methods in Drosophila melanogaster showed that both drugs possess the mutagenic activity. The comparison of the data obtained for both drugs by the methods of recessive, sex-linked, lethal mutations and somatic mosaicism indicates the quantitative and qualitative similarity of their mutagenic action. The results make it possible to regard the method of somatic mosaicism as a promising test for primary evaluation of mutagenic properties of chemical compounds.
