An Electronic Information Kiosk for Enhancing Patient Accrual for Cancer Clinical Trials: A Pilot and Feasibility Study.

Introduction Low accrual to clinical trials for solid tumors at our institution led to a review of possible modifiable factors within our control. This led to a pilot project to determine whether improved patient awareness could alter accrual rates to active trials. Methods An information kiosk was located at the patient library on the ground floor of the London Regional Cancer Program. Adult cancer patients were invited to learn more about clinical trials from our research navigator, including specific trials open in our center, and to participate in the study, which involved a brief satisfaction and demographics survey. Results Three hundred and eighty-six (386) patients interacted with the clinical trial information kiosk over the eight weeks it was open. Of these, 32 patients consented and filled out surveys, which indicated an overall positive interaction with the kiosk. Unfortunately, in the time period examined, clinical trial accrual rates appeared to decrease when the pre- and post-kiosk activation periods were compared (44 versus 37 patients accrued to various trials). Conclusion Our pilot study found that the implementation of a clinical trial information kiosk was easy to understand and useful for patients to learn more about clinical trials. Barriers to this patient satisfaction translating into increased accrual rates in our center included suboptimal kiosk location and lack of guidance to the kiosk from clerical staff. High patient satisfaction scores support the potential value of permanent clinical trial information kiosks in our cancer center, but this requires increased attention to visibility, location, and staff education.

BReast CAncer susceptibility gene 2 deficiency exacerbates oxidized LDL-induced DNA damage and endothelial apoptosis.

Mutations in the tumor suppressor gene BRCA2 (BReast CAncer susceptibility gene 2) predispose carriers to breast, ovarian, and other cancers. In response to DNA damage, BRCA2 participates in homology-directed DNA damage repair to maintain genome stability. Genome-wide association studies have identified an association between BRCA2 single nucleotide polymorphisms and plasma-lipid levels and lipid deregulation in humans. To date, DNA damage, apoptosis, and lipid deregulation are recognized as central pathways for endothelial dysfunction and atherosclerosis; however, the role of BRCA2 in endothelial dysfunction remains to be elucidated. To determine the role of BRCA2 in endothelial dysfunction, BRCA2 was silenced in human umbilical vein endothelial cells (ECs) and assessed for markers of DNA damage, apoptosis, and endothelial function following oxidized low-density lipoprotein (oxLDL) treatment. OxLDL was found to induce significant reactive oxygen species (ROS) production in BRCA2-silenced ECs. This increase in ROS production was associated with exacerbated DNA damage evidenced by increased expression and activation of DNA double-stranded break (DSB) marker γH2AX and reduced RAD51-foci formation-an essential regulator of DSB repair. Increased DSBs were associated with enhanced expression and activation of pro-apoptotic p53 and significant apoptosis in oxLDL-treated BRCA2-silenced ECs. Loss of BRCA2 in ECs was further associated with oxLDL-induced impaired tube-forming potential and eNOS expression. Collectively, the data reveals, for the first time, a novel role of BRCA2 as a regulator of EC survival and function in the setting of oxLDL treatment in vitro. Additionally, the data provide important clues regarding the potential susceptibility of BRCA2 mutation carriers to endothelial dysfunction, atherosclerosis, and other cardiovascular diseases.