The antitumor immune response in HER-2 positive, metastatic breast cancer patients

The aim of this study was to determine the basis for anti-tumor immune reactivity observed in patients with human epidermal growth factor receptor-2 (HER-2) (3+) breast carcinoma using an in vitro model in which the role of the HER-2-specific monoclonal antibody Herceptin was also investigated. Patients with metastatic breast cancer who had their primary tumor resected were included in this study. Peripheral blood mononuclear cell (PBMC)-dependent cytotoxicity in the presence or absence of Herceptin were assessed using the survival of target breast adenocarcinoma MDA-MB-361 cells as a parameter in a (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) test. We observed a significant increase in PBMC-dependent cytotoxicity when autologous serum was introduced in the assay. Furthermore, the addition of Herceptin significantly increases their cytotoxicity. These data suggest that autologous serum constitutively contains factors that might affect PBMC-dependent cytotoxic activity against HER-2 positive cancer cells

Threading of Conformationally Stable Calix[6]arene Wheels Substituted at the Methylene Bridges

Calix[6]arenes disubstituted at the methylene bridges, which are stable in the cone or 1,2,3-alternate conformation, form pseudorotaxanes with dialkylammonium axles. The cone wheel-based pseudorotaxanes are 10-100 times more stable than those obtained with the native conformationally mobile calix[6]arene wheel, as a consequence of their higher degree of preorganization. The threading of conformationally stable 1,2,3-alternate calix[6]arenes is unprecedented in the literature. Therefore, very peculiar NMR features are here evidenced for this threading process involving the less symmetrical 1,2,3-alternate calix[6]arene conformation, which implies a peculiar rototranslation motion of the axle

Estimation of scattered radiation in digital breast tomosynthesis

Digital breast tomosynthesis (DBT) is a promising technique to overcome the tissue superposition limitations found in planar 2D x-ray mammography. However, as most DBT systems do not employ an anti-scatter grid, the levels of scattered radiation recorded within the image receptor are significantly higher than that observed in planar 2D x-ray mammography. Knowledge of this field is necessary as part of any correction scheme and for computer modelling and optimisation of this examination. Monte Carlo (MC) simulations are often used for this purpose, however they are computationally expensive and a more rapid method of calculation is desirable. This issue is addressed in this work by the development of a fast kernel-based methodology for scatter field estimation using a detailed realistic DBT geometry. Thickness-dependent scatter kernels, which were validated against the literature with a maximum discrepancy of 4% for an idealised geometry, have been calculated and a new physical parameter (air gap distance) was used to estimate more accurately the distribution of scattered radiation for a series of anthropomorphic breast phantom models. The proposed methodology considers, for the first time, the effects of scattered radiation from the compression paddle and breast support plate, which can represent more than 30% of the total scattered radiation recorded within the image receptor. The results show that the scatter field estimator can calculate scattered radiation images in an average of 80 min for projection angles up to 25° with equal to or less than a 10% error across most of the breast area when compared with direct MC simulations

Identifying and modelling clinical subpopulations from the Malmö breast tomosynthesis screening trial

Virtual Clinical Trials (VCT) are an effective tool to evaluate the performance of novel imaging systems using computer simulations. VCT results depend on the selection of virtual patient populations. In the case of breast imaging, virtual patients should be matched to a desired clinical population in terms of selected anatomical or demographic descriptors. We are developing a virtual population of women who participated in the Malmö Breast Tomosynthesis Screening Trial (MBTST). We have used clinical values of the compressed breast thickness and volumetric breast density to develop a multidimensional distribution of women in MBTST. Breast density and thickness values were obtained from anonymized, previously collected tomosynthesis images of 14,746 women. In this paper, we compare several approaches to identify clinical subpopulations and select virtual patients that represent various groups of clinical subjects. We performed two methods to identify clinical subpopulations by clustering clinical data using the K-means algorithm or woman's age. The obtained clusters have been explored and compared using the silhouette mean. The K-means algorithm yielded grouping of MBTST data into two clusters; however, that grouping was, shown to be suboptimal by the silhouette analysis. The agebased clustering showed significant overlap in terms of breast thickness and density. We also compared two approaches to select sets of representative phantoms. Our analysis has emphasized benefits and limitations of different clustering methods. The preferred method depends on the specific task that should be addressed using VCTs. Simulation of representative phantoms is ongoing. Potential correlations with pathological findings and/or parenchymal properties will be investigated