Enhancement of radiation response by roscovitine in human breast carcinoma in vitro and in vivo.

Frequent deregulation of cyclin-dependent kinase (CDK) activation associated with loss of cell cycle control was found in most of human cancers. A recent development of a new class of antineoplasic agents targeting the cell cycle emerged as a small molecule CDK inhibitor, roscovitine, which presents potential antiproliferative and antitumoral effects in human tumors. Additional studies reported that roscovitine combined with cytotoxic agents can cooperate with DNA damage to activate p53 protein.

Use of the Kohonen neural network for rapid screening of ex vivo anti-HIV activity of styrylquinolines.

Using the Kohonen neural network, the electrostatic potentials on the molecular surfaces of 14 styrylquinoline derivatives were drawn as comparative two-dimensional maps and compared with their known human immunodeficiency virus (HIV)-1 replication blocking potency in cells. A feature of the potential map was discovered to be related with the HIV-1 blocking activity and was used to unmask the activity of further five analogues, previously described but whose cytotoxicity precluded an estimation of their activity, and to predict the activity of 10 new compounds while the experimental data were unknown. The measurements performed later turned out to agree with the predictions.

Effect of Ku80 depletion on the preintegrative steps of HIV-1 replication in human cells.

To gain new insights regarding the role of Ku, the DNA-PK DNA-binding component, during lentiviral DNA integration, we have investigated the HIV-1 replication in Ku80-depleted human cells. CEM4fx cells underexpressing the Ku80 factor were selected after transduction by a retroviral vector expressing the Ku80 full-length antisense sequence. De novo infection experiment with NL4.

Ku represses the HIV-1 transcription: identification of a putative Ku binding site homologous to the mouse mammary tumor virus NRE1 sequence in the HIV-1 long terminal repeat.

Ku has been implicated in nuclear processes, including DNA break repair, transcription, V(D)J recombination, and telomere maintenance. Its mode of action involves two distinct mechanisms: one in which a nonspecific binding occurs to DNA ends and a second that involves a specific binding to negative regulatory elements involved in transcription repression. Such elements were identified in mouse mammary tumor virus and human T cell leukemia virus retroviruses.