Purpose The Dutch MRI Screening Study on early detection of hereditary breast cancer started in 1999. We evaluated the long-term results including separate analyses of BRCA1 and BRCA2 mutation... Show morePurpose The Dutch MRI Screening Study on early detection of hereditary breast cancer started in 1999. We evaluated the long-term results including separate analyses of BRCA1 and BRCA2 mutation carriers and first results on survival. Patients and Methods Women with higher than 15% cumulative lifetime risk (CLTR) of breast cancer were screened with biannual clinical breast examination and annual mammography and magnetic resonance imaging (MRI). Participants were divided into subgroups: carriers of a gene mutation (50% to 85% CLTR) and two familial groups with high (30% to 50% CLTR) or moderate risk (15% to 30% CLTR). Results Our update contains 2,157 eligible women including 599 mutation carriers (median follow-up of 4.9 years from entry) with 97 primary breast cancers detected (median follow-up of 5.0 years from diagnosis). MRI sensitivity was superior to that of mammography for invasive cancer (77.4% v 35.5%; P < .00005), but not for ductal carcinoma in situ. Results in the BRCA1 group were worse compared to the BRCA2, the high-, and the moderate-risk groups, respectively, for mammography sensitivity (25.0% v 61.5%, 45.5%, 46.7%), tumor size at diagnosis <= 1 cm (21.4% v 61.5%, 40.9%, 63.6%), proportion of DCIS (6.5% v 18.8%, 14.8%, 31.3%) and interval cancers (32.3% v 6.3%, 3.7%, 6.3%), and age at diagnosis younger than 30 years (9.7% v 0%). Cumulative distant metastasis-free and overall survival at 6 years in all 42 BRCA1/2 mutation carriers with invasive breast cancer were 83.9% (95% CI, 64.1% to 93.3%) and 92.7% (95% CI, 79.0% to 97.6%), respectively, and 100% in the familial groups (n = 43). Conclusion Screening results were somewhat worse in BRCA1 mutation carriers, but 6-year survival was high in all risk groups. Show less
We use the polyhedral process network (PPN) model of computation to program and map streaming applications onto embedded Multi-Processor Systems on Chip (MPSoCs) platforms. The PPNs, which can be... Show moreWe use the polyhedral process network (PPN) model of computation to program and map streaming applications onto embedded Multi-Processor Systems on Chip (MPSoCs) platforms. The PPNs, which can be automatically derived from sequential program applications, do not necessarily meet the performance/resource constraints. A designer can therefore apply the process splitting transformations to increase program performance, and the process merging transformation to reduce the number of processes in a PPN. These transformations were defined, but a designer had many possibilities to apply a particular transformation, and these transformations can also be ordered in many different ways. In this dissertation, we define compile-time solution approaches that assist the designer in evaluating and applying process splitting and merging transformations in the most effective way. Show less
G.J. van der bij; Bogels, M.; Otten, M.A.; Oosterling, S.J.; Kuppen, P.J.; Meijer, S.; ... ; Egmond, M. van 2010
Background 82 Aims: Development of liver metastases is a frequent complication in patients with colorectal cancer (CRC), even after successful resection of the primary tumor. As such, postoperative... Show moreBackground 82 Aims: Development of liver metastases is a frequent complication in patients with colorectal cancer (CRC), even after successful resection of the primary tumor. As such, postoperative adjuvant therapies that aim to eliminate residual disease after surgery may improve patient outcome. Methods: We used a colon carcinoma liver metastases model, in which CC531s colon carcinoma cells are injected into the portal circulation by a surgical procedure. As injected tumor cells are arrested in the liver, this model is suitable for investigating the interaction of tumor cells with the liver microenvironment. By administering tumor specific monoclonal antibodies (mAb) directly post-operatively, we were able to determine the effect of antibody therapy on eradication of arrested tumor cells and subsequent liver metastases outgrowth. Results: We showed that post-operative treatment with tumor specific monoclonal antibodies (mAb) prevents liver metastases outgrowth. Antibody-dependent phagocytosis (ADPh) was the main mechanism involved, as enhanced uptake of tumor cells by innate mononuclear phagocytes in the liver was observed after mAb therapy. Furthermore, Kupffer cells (KC) were identified as the most prominent effector cells, as depletion of KC abolished therapeutic efficacy. This was partly compensated by monocytes when animals were treated with a high mAb dose, but monocytes were unable to phagocytose tumor cells when rats were treated with low mAb doses. Conclusions: The finding that KC and monocytes can eliminate tumor cells through ADPh has important and promising clinical implications for designing new adjuvant therapies for patients undergoing CRC resection. (C) 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. Show less
