they examined reference lists for eligible articles. Titles and abstracts were reviewed to identify relevant studies. Data on barriers to participation were synthesized both qualitatively and based on statistically significant associations with trial enrollment. Of 5257 studies that were cited, 65 studies were eligible for inclusion in the current analysis, including 46 studies on recruitment into cancer therapeutic trials, 15 studies on recruitment into prevention trials, and 4 studies on recruitment into both prevention and treatment trials. Numerous factors were reported as barriers to participation in cancer-related trials. However, only 20 of the studies reported statistically significant associations between hypothesized barriers and enrollment. The available evidence had limitations in quality regarding representativeness, justification of study methods, the reliability and validity of data-collection methods, potential for bias, and data analysis. The results indicate that underrepresented populations face numerous barriers to participation in cancer-related trials. The current systematic review highlighting the literature on recruitment of underrepresented populations to cancer trials and may be used as the evidence base toward developing an agenda for etiologic and intervention research to reduce the disparities in participation in cancer-related trials. Cancer ;112:228-42. 2008

BACKGROUND.Providers play a vital role in the successful recruitment of underrepresented patients to cancer clinical trials because they often introduce the opportunity of clinical trials. The purpose of the current systematic review was to describe provider‐related factors influencing recruitment of underrepresented populations to cancer clinical trials.METHODS.To find original studies on the recruitment of underrepresented populations to cancer clinical trials, electronic databases from January 1966 to December 2005 were searched; hand‐searched titles in 34 journals from January 2003 to January 2006; and reference lists were examined of eligible articles. Title and abstract reviews were conducted to identify relevant studies. Potential articles were then abstracted using a structured instrument and a serial review process by 2 investigators.RESULTS.Eighteen studies were eligible for review: 13 targeted healthcare providers, 3 targeted patients/participants, and 2 targeted both providers and patients. The study designs included randomized controlled trial, concurrent controlled trial, case‐control, descriptive, and qualitative. A lack of available protocols and/or a lack of provider awareness about clinical trials prevented providers from discussing the opportunity of clinical trials in 2 studies. In 14 studies, patient accrual was affected by provider attitudinal barriers relating to patient adherence to the study protocol, patient mistrust of research, patient costs, data collection costs, and/or patient eligibility. Providers' communication methods were barriers in 5 studies and promoters in 1 study.CONCLUSIONS.A heterogeneous body of evidence suggests that several provider‐related factors influence recruitment of underrepresented groups to clinical trials. Future recruitment efforts should address these factors. Cancer 2007;109:465–476. © 2007 American Cancer Society.

Neuroblastomas, an embryonic cancer of the sympathetic nervous system, often occur in young children. Honokiol, a small-molecule polyphenol, has multiple therapeutic effects and pharmacological activities. This study was designed to evaluate whether honokiol could pass through the blood-brain barrier (BBB) and induce death of neuroblastoma cells and its possible mechanisms. Primary cerebral endothelial cells (CECs) prepared from mouse brain capillaries were cultured at a high density for 4 days, and these cells formed compact morphologies and expressed the ZO-1 tight-junction protein. A permeability assay showed that the CEC-constructed barrier obstructed the passing of FITC-dextran. Analyses by high-performance liquid chromatography and the UV spectrum revealed that honokiol could traverse the CEC-built junction barrier and the BBB of ICR mice. Exposure of neuroblastoma neuro-2a cells and NB41A3 cells to honokiolinduced cell shrinkage and decreased cell viability. In parallel, honokiol selectively induced DNA fragmentation and cell apoptosis rather than cell necrosis. Sequential treatment of neuro-2a cells with honokiol increased the expression of the proapoptotic Bax protein and its translocation from the cytoplasm to mitochondria. Honokiol successively decreased the mitochondrial membrane potential but increased the release of cytochrome c from mitochondria. Consequently, honokiol induced cascade activation of caspases-9, -3, and -6. In comparison, reducing caspase-6 activity by Z-VEID-FMK, an inhibitor of caspase-6, simultaneously attenuated honokiol-induced DNA fragmentation and cell apoptosis. Taken together, this study showed that honokiol can pass through the BBB and induce apoptotic insults to neuroblastoma cells through a Bax-mitochondrion-cytochrome c-caspase protease pathway. Therefore, honokiol may be a potential candidate drug for treating brain tumors.