Federico Focher

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Several cytokines and growth factors modulate angiogenesis through a fine tuned paracrine or autocrine mode of action. Among them is plateled-derived endothelial cell growth factor (PD-ECGF), which is highly is expressed in tumors, and is angiogenic by stimulation of endothelial cell migration. Studies have shown that PD-ECGF is identical to the well known(More)
The activity of nuclear DNA polymerases alpha, beta and delta/epsilon, uracil-DNA glycosylase, thymidine kinase and the presence of Proliferating Cell Nuclear Antigen (PCNA) have been examined in developing rat glial cells, in rat and human glioma, in human neuroblastoma and in differentiated neuroblastoma cell lines in vitro. During glial development the(More)
We have shown that DNA polymerase beta, the only nuclear DNA polymerase present in adult neurons, cannot discriminate between dTTP and dUTP, having the same Km for both substrates. This fact suggests that during reparative DNA synthesis, in adult neurons, dUMP residues can be incorporated into DNA. Since uracil DNA-glycosylase functions to prevent the(More)
We have recently demonstrated that mammalian uracil-DNA glycosylase activity is undetectable in adult neurons. On the basis of this finding we hypothesized that uracil, derived either from oxidative deamination of cytosine or misincorporation of dUMP in place of dTMP during DNA repair by the unique nuclear DNA polymerase present in adult neurons, DNA(More)
Herpes B virus (B virus [BV]) is a macaque herpesvirus that is occasionally transmitted to humans where it can cause rapidly ascending encephalitis that is often fatal. To understand the low susceptibility of BV to the acyclonucleosides, we have cloned, expressed, and characterized the BV thymidine kinase (TK), an enzyme that is expected to "activate"(More)
Cellular factors may contribute to the decreased efficacy of chemotherapy in HIV infection. Indeed, prolonged treatment with nucleoside analogues, such as azidothymidine (AZT), 2',3'-deoxycytidine or 9-(2-phosphonylmethoxyethyl)adenine, induces cellular resistance. We have developed a human T lymphoblastoid cell line (CEM 3TC) that is selectively resistant(More)
Quantitative effects of inhibitors of the replicative DNA polymerases (pol) alpha, delta and epsilon from calf thymus are reported under similar assay conditions. Carbonyldiphosphonate was a competitive inhibitor of pols delta and epsilon, with 4- to 6-fold selectivity compared to pol alpha. Aphidicolin inhibited pols alpha and delta with 6- to 10-fold(More)
Aphidicolin inhibits DNA replication and growth of all tested human and murine neoplastic cells including leukemic T- and B-lymphocytes and melanocarcinoma cells. The concentration of aphidicolin causing 50% inhibition of DNA synthesis in all of the tested neoplastic cell lines is similar to that necessary to inhibit DNA synthesis in HeLa cells by 50%. The(More)
Thymidine phosphorylase/platelet-derived endothelial cell growth factor (TP/PD-ECGF) is an enzyme involved in thymidine metabolism and homeostasis, and its catalytic activity appears to play an important role in angiogenesis. Here we describe the cloning and expression of a His-tagged human TP/PD-ECGF and its assay with uracil and thymine analogues. We(More)
We have purified Herpes simplex type 1 (HSV1) uracil-DNA glycosylase from the nuclei of HSV1-infected HeLa cells harvested 8 h post-infection, at which time the induction of the enzyme is a maximum. The enzyme has been shown to be distinct from the host enzyme, isolated from HeLa cells, by its lack of sensitivity to a monoclonal antibody to human uracil-DNA(More)