Childhood, adolescent, and young adult cancer survivors research program of British Columbia: objectives, study design, and cohort characteristics.

BACKGROUND: The Childhood, Adolescent, and Young Adult Cancer Survivors Research Program (CAYACS) has been established in the province of British Columbia (BC), Canada, to carry out research into late effects and survivor care in multiple domains, and to inform policy and practice. PROCEDURE: This program identifies a survivor cohort and comparison groups from population-based registries and links their records to population-based files of outcomes and outcome determinants, to create a research database and conduct studies of long-term outcomes and care. RESULTS: The initial cohort consisted of all 5-year survivors of cancer or a tumor diagnosed under age 25 years from 1970 to 1995, who were residents in BC at the time of diagnosis, and followed till 2000 (3,841 subjects). Seven percent have died, and 77% have treatment information available. Data on death and second cancer occurring in BC are available. Late morbidity and healthcare utilization information is available for 68% of survivors (79% of those diagnosed from 1981). Education outcomes are available for 71% of those born during 1978-1995 and diagnosed under age 15 years. CONCLUSIONS: Use of registries, administrative databases, and record linkage methodologies is a cost-effective and comprehensive means to conduct survivorship research. This program should add to knowledge of risks of late effects and impacts on care, inform development of strategies to manage risks, evaluate the effects of surveillance and interventions, and assess new risks as the cohort ages, more recent survivors enter the cohort, and treatments change.

Vascular endothelial growth factor expression and signaling in the lens.

PURPOSE: Previous studies have identified sequences encoding vascular endothelial growth factor (VEGF)-A and one of the VEGF receptors (VEGFR2, Flk-1, KDR) in lens fiber cells. The current study was undertaken to determine the distribution of VEGF-A protein in the lens, whether signaling through VEGF receptors occurs in lens cells, the pattern of VEGF-A expression during lens development, and the effect of hypoxia on VEGF-A expression. METHODS: VEGF-A and VEGFR2 were localized using immunocytochemistry. VEGF-A and VEGFR2 protein were identified and quantified by Western blot analysis. Activated (tyrosine phosphorylated) VEGFR2 was detected by immunoprecipitation with an anti-phosphotyrosine antibody followed by Western blot analysis with antibody to VEGFR2. Levels of VEGF-A mRNA were measured by quantitative PCR. Suturing the lids of adult mouse or rabbit eyes for 3 days was used to induce lens hypoxia. RESULTS: VEGFR2 sequences were present in adult human lens epithelial cells, and VEGF-A transcripts were detected in chicken embryo, adult human, and mouse lens epithelial cells. VEGF-A protein localized to the ends of mouse embryo lens fiber cells at developmental stages when the fetal vasculature was forming. At later stages, VEGF-A was distributed uniformly throughout the cytoplasm of cortical fiber cells. VEGFR2 was present in mouse lens epithelial and fiber cells and was tyrosine phosphorylated at all stages examined. VEGF-A protein was barely detectable in lens epithelial cells during the first postnatal week, but increased as the capillaries of the anterior pupillary membrane regressed. VEGF-A levels were highest in adult lenses. Suturing the eyelid caused an increase in VEGF-A mRNA and protein in lens epithelial and fiber cells. CONCLUSIONS: VEGF-A secreted by lens cells may stimulate the formation of the fetal vasculature, but regression of these vessels is not likely to be caused by a reduction in VEGF-A production by the lens. An active VEGF-A signaling system of unknown function appears to be active in the lens. It is likely that VEGF-A expression is regulated by tissue hypoxia at all stages of lens development.