We have demonstrated that designed ankyrin repeat protein (DARPin) _9-29, which specifically targets human epidermal growth factor receptor 2 (HER2), binds tightly to gold mini nanorods (GNRs). Molecular dynamic simulations showed that a single layer of DARPin_9-29 molecules is formed on the surface of the nanorod and that conjugation with the nanorod does not involve the protein's domain responsible for specific binding to HER2. The nanorod-DARPin (DARPin-GNR) conjugate is specifically bound (in nanomolar concentrations) to human breast adenocarcinoma SK-BR-3 cells overexpressing HER2. Illumination by near-infrared light (850 nm) led to almost complete eradication of the conjugate-treated SK-BR-3 cells; the viability of epithelial human breast cancer cells expressing normal amounts of the receptor was much less affected by the illumination. The results reported here pave the way toward application of DARPin-GNR conjugates in phototherapy of cancer.
206 Background: Cancer screening, like other interventions, requires close patient-provider collaboration. By patient recall, key elements are often omitted from informed consent discussions. Most screening guideline compliance efforts focus on reducing underuse, but overuse is also harmful and may be influenced by distinct factors. Therefore, we are performing a prospective randomized trial of educational interventions to improve screening compliance for breast, cervical, colorectal, lung and prostate cancer at an urban academic medical center. Our hypothesis is that gender, age, prior screening experience, provider recommendations, anticipated benefit and distress, communication and informational support will affect compliance. Our primary data collection will be complete before the Symposium. Methods: We will enroll an age- and sex-stratified sample of 216 patients aged 40 to 89 years, 18 each treated by 12 primary care physicians at two affiliated hospitals, undergoing an annual physical examination in a cluster-randomized prospective trial of educational supports for screening. Screening guideline format (color-coding) and academic detailing will be randomly assigned independently. Patients and providers are surveyed immediately after the encounter to record their recollections of screening discussions and recommendations and their plans. Follow-up surveys at 3, 6 and 12 months assess concordance between expressed screening intentions and behaviors. Results: Pilot results indicate patient gender, age, anticipated screening-related distress and benefit, and prior screening experience affect screening recommendations and intentions. These factors vary by cancer. Patients recall less discussion than providers. Reasons not to screen are infrequently discussed. Conclusions: Cancer screening decisions are complex and vary by screening modality, patient and provider factors and communication. Improving underuse and overuse compliance may require distinct strategies. Screening overuse may be a “lower-stakes” environment to develop strategies to reduce overuse of cancer interventions of marginal or negative benefit, including treatment.
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