The authors describe a rabbit arterial thrombosis model that employs vessel division followed by microsurgical anastomosis and transluminal sutures, to reliably induce thrombus formation in the common femoral artery (CFA). Using two objective measures, "evacuation/refill" evaluation of patency and computer-aided histomorphometric analysis of the thrombus area, thrombus formation was confirmed and characterized in the model at both short- and long-term observation time-points. In addition, a gene delivery method was developed in the CFA that employs an adenoviral vector solution injected through the inferior epigastric artery (IEA). Using this method, a marker transgene (beta-galactosidase) was delivered to endothelial cells locally and without trauma. By subsequently performing beta-galactosidase staining, effective endothelial transfection was demonstrated simultaneously with endothelial viability, with preserved endothelial synthetic function in the immediate environment of the occluding thrombus. The results suggest that these two techniques can be used together in one model, to effectively introduce a foreign therapeutic transgene into endothelial cells and to evaluate the effect of the expressed protein product in a consistent in vivo thrombosis system. This combined model may be used as one of several assays of efficacy in future endothelial cell-targeted thrombolytic/antithrombotic vascular gene therapy research.
6016 Background: Current estimates are less than 5% of adult cancer patients participate in clinical trials. Initiatives to address barriers to accrual (such as age, physician bias, etc) are ongoing. However, with more drugs in the pipeline and more clinical trials being conducted, demand for trial participants may be outpacing the current “supply”. Methods: The ClinicalTrials.gov database, maintained by National Institutes of Health was selected for review on the basis that it is proposed to be the mandated repository for clinical trials information. Over a 2 month period, the database was mined for all active, US recruiting, phase I, I/II, II, and III trials in breast, lung, and prostate cancers. Results: There were 290 breast, 212 lung, and 177 prostate cancer trials with the prespecified criteria. The number of patients needed to complete these trials is 151,311 (breast), 33,498 (lung), and 53,181 (prostate). These represent 19.4% to 71.6% of the American Cancer Society incidence estimates of the studied tumors. NCI, industry, and academia sponsored, either solely or in collaborations, 42.1%, 26.5%, and 45.6% of trials, respectively. Majority of studies were phase II (51%), with 11.5% phase I, and 15.6% phase III. Remaining studies were either combined phase I/II studies or not specified. Significant percentage of trials involved pts with advanced/metastatic disease (54% breast, 51.4% lung, and 44.6% prostate). Conclusions: Although many studies have anticipated enrollment period over several years, the number of trial participants needed to complete these studies is quite daunting. Our results are likely under-estimates as not all studies currently enrolling patients may be included in this registry, and not all studies in the database specified the recruitment goal. Although not all trial participants are drawn from the incidence numbers, it is clear that given the current trial participation rate, demand has outpaced the supply. The medical community has the ethical responsibility to ensure sufficient patient enrollment for clinical trials. In addition to addressing accrual barriers, the authors encourage the establishment of a task force including academia, government, and industry to systematically evaluate and prioritize the types of trials being conducted. No significant financial relationships to disclose.
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