Since early in the Atomic Age, biological indicators of radiation exposure have been sought, but currently available methods are not entirely satisfactory. Using cDNA microarray hybridization to discover new potential biomarkers, we have identified genes expressed at increased levels in human peripheral blood lymphocytes after ex vivo irradiation. We recently used this technique to identify a large set of ionizing radiation-responsive genes in a human cell line (Oncogene 18, 3666-3672, 1999). The present set of radiation markers in peripheral blood lymphocytes was identified 24 h after treatment, and while the magnitude of mRNA induction generally decreased over time, many markers were still significantly elevated up to 72 h after irradiation. In all donors, the most highly responsive gene identified was DDB2, which codes for the p48 subunit of XPE, a protein known to play a crucial role in repair of ultraviolet (UV) radiation damage in DNA. Induction of DDB2, CDKN1A (also known at C1P1/WAF1) and XPC showed a linear dose-response relationship between 0.2 and 2 Gy at 24 and 48 h after irradiation, with less linearity at earlier or later times. These results suggest that relative levels of gene expressions in peripheral blood cells may provide estimated of environmental radiation exposures.

Coordinated regulation of the actin cytoskeleton is central to cell motility, invasion and metastasis. Head and neck squamous cell carcinoma (HNSCC) is a highly invasive disease displaying frequent lymph node metastasis, compounding patient management. HNSCC progression is characterized by frequent amplification of chromosome segments 3q26-29, 8q23-24 and 11q13, events that are associated with poor patient outcome. The relative frequency of these amplification events and correlation with invasive disease raises the potential that these regions harbor actin regulatory genes important in facilitating reorganization of the actin cytoskeleton to promote tumor invasion. Identification of the actin cytoskeletal regulatory genes located within the 3q26-29, 8q23-24 and 11q13 amplicons will provide an important first step towards the comprehensive understanding of the molecular events that govern invasion and metastasis in HNSCC and other tumors containing these amplifications. We utilized Ensembl MartView to conduct a gene mining analysis within chromosome segments 3q26-29, 8q23-24 and 11q13 to identify known and predicted regulators of actin-based cell movement, tumor invasion and metastasis. All examined chromosomal regions contain genes known that regulate the actin cytoskeleton, with several (PI3-kinase alpha, focal adhesion kinase (FAK) and cortactin) known to promote invasion in HNSCC and other carcinomas. Additional genes known to regulate motility and invasion were also identified. Amplification of chromosome 3q26-29, 8q23-24 and 11q13 therefore results in known or predicted overexpression of several key mediators that can act alone or potentially act in concert to promote actin-based cell invasion in HNSCC and other cancer types.

Because the incidence of S. pneumoniae was low, no inference could be made whether Prevnar decreased otitis media with effusion or recurrent acute otitis caused by the S. pneumoniae serotypes covered by the vaccine. However, vaccinated children did appear to have the unexpected benefit of having a certain level of protection to growth of typical acute otitis media pathogens.

No abstract