Dipole anisotropies of IRAS galaxies and the contribution of a large-scale local void

Recent observations of dipole anisotropies show that the velocity of the Local Group (\Vec v_{\rm G}) induced by the clustering of IRAS galax ies has an amplitude and direction similar to those of the velocity of Cosmic Microwave Background dipole anisotropy (\Vec v_{\rm CMB}), but the difference | \Vec v_{\rm G} - \Vec v_{\rm CMB} | is still $\sim 170$ km/s, which is about 28% of |\Vec v_{\rm CMB} |. Here we consider the possibility that the origin of this difference comes from a hypothetical large-scale local void, with which we can account for the accelerating behavior of type Ia supernovae due to the spatial inhomogeneity of the Hubble constant without dark energies and derive the constraint to the model parameters of the local void. It is found as a result that the distance between the Local Group and the center of the void must be $(10 -- 20) h^{-1}$ Mpc, whose accurate value depends on the background model parameters.Comment: 13 pages, 1 figure, to be published in ApJ 584, No.2 (2003

Observable Isocurvature Fluctuations from the Affleck-Dine Condensate

In D-term inflation models, Affleck-Dine baryogenesis produces isocurvature density fluctuations. These can be perturbations in the baryon number, or, in the case where the present neutralino density comes directly from B-ball decay, perturbations in the number of dark matter neutralinos. The latter case results in a large enhancement of the isocurvature perturbation. The requirement that the deviation of the adiabatic perturbations from scale invariance due to the Affleck-Dine field is not too large then imposes a lower bound on the magnitude of the isocurvature fluctuation of about $10^{-2}$ times the adiabatic perturbation. This should be observable by MAP and PLANCK.Comment: LaTex 9 pages, 1 Figur

Dense breast stromal tissue shows greatly increased concentration of breast epithelium but no increase in its proliferative activity

INTRODUCTION: Increased mammographic density is a strong risk factor for breast cancer. The reasons for this are not clear; two obvious possibilities are increased epithelial cell proliferation in mammographically dense areas and increased breast epithelium in women with mammographically dense breasts. We addressed this question by studying the number of epithelial cells in terminal duct lobular units (TDLUs) and in ducts, and their proliferation rates, as they related to local breast densities defined histologically within individual women. METHOD: We studied deep breast tissue away from subcutaneous fat obtained from 12 healthy women undergoing reduction mammoplasty. A slide from each specimen was stained with the cell-proliferation marker MIB1. Each slide was divided into (sets of) areas of low, medium and high density of connective tissue (CT; highly correlated with mammographic densities). Within each of the areas, the numbers of epithelial cells in TDLUs and ducts, and the numbers MIB1 positive, were counted. RESULTS: The relative concentration (RC) of epithelial cells in high compared with low CT density areas was 12.3 (95% confidence interval (CI) 10.9 to 13.8) in TDLUs and 34.1 (95% CI 26.9 to 43.2) in ducts. There was a much smaller difference between medium and low CT density areas: RC = 1.4 (95% CI 1.2 to 1.6) in TDLUs and 1.9 (95% CI 1.5 to 2.3) in ducts. The relative mitotic rate (RMR; MIB1 positive) of epithelial cells in high compared with low CT density areas was 0.59 (95% CI 0.53 to 0.66) in TDLUs and 0.65 (95% CI 0.53 to 0.79) in ducts; the figures for the comparison of medium with low CT density areas were 0.58 (95% CI 0.48 to 0.70) in TDLUs and 0.66 (95% CI 0.44 to 0.97) in ducts. CONCLUSION: Breast epithelial cells are overwhelmingly concentrated in high CT density areas. Their proliferation rate in areas of high and medium CT density is lower than that in low CT density areas. The increased breast cancer risk associated with increased mammographic densities may simply be a reflection of increased epithelial cell numbers. Why epithelium is concentrated in high CT density areas remains to be explained

Relationship between morphological features and kinetic patterns of enhancement of the dynamic breast magnetic resonance imaging and clinico-pathological and biological factors in invasive breast cancer

<p>Abstract</p> <p>Background</p> <p>To investigate the relationship between the magnetic resonance imaging (MRI) features of breast cancer and its clinicopathological and biological factors.</p> <p>Methods</p> <p>Dynamic MRI parameters of 68 invasive breast carcinomas were investigated. We also analyzed microvessel density (MVD), estrogen and progesterone receptor status, and expression of p53, HER2, ki67, VEGFR-1 and 2.</p> <p>Results</p> <p>Homogeneous enhancement was significantly associated with smaller tumor size (T1: < 2 cm) (p = 0.015). Tumors with irregular or spiculated margins had a significantly higher MVD than tumors with smooth margins (p = 0.038). Tumors showing a maximum enhancement peak at two minutes, or longer, after injecting the contrast, had a significantly higher MVD count than those which reached this point sooner (p = 0.012). The percentage of tumors with vascular invasion or high mitotic index was significantly higher among those showing a low percentage (≤ 150%) of maximum enhancement before two minutes than among those ones showing a high percentage (>150%) of enhancement rate (p = 0.016 and p = 0.03, respectively). However, there was a significant and positive association between the mitotic index and the peak of maximum intensity (p = 0.036). Peritumor inflammation was significantly associated with washout curve type III (p = 0.042).</p> <p>Conclusions</p> <p>Variations in the early phase of dynamic MRI seem to be associated with parameters indicatives of tumor aggressiveness in breast cancer.</p

Breast imaging technology: Application of magnetic resonance imaging to angiogenesis in breast cancer

Magnetic resonance imaging (MRI) techniques enable vascular function to be mapped with high spatial resolution. Current methods for imaging in breast cancer are described, and a review of recent studies that compared dynamic contrast-enhanced MRI with histopathological indicators of tumour vascular status is provided. These studies show correlation between in vivo dynamic contrast measurements and in vitro histopathology. Dynamic contrast enhanced MRI is also being applied to assessment of the response of breast tumours to treatment

Mammographic density does not correlate with Ki-67 expression or cytomorphology in benign breast cells obtained by random periareolar fine needle aspiration from women at high risk for breast cancer

BACKGROUND:Ki-67 expression is a possible risk biomarker and is currently being used as a response biomarker in chemoprevention trials. Mammographic breast density is a risk biomarker and is also being used as a response biomarker. We previously showed that Ki-67 expression is higher in specimens of benign breast cells exhibiting cytologic atypia that are obtained by random periareolar fine needle aspiration (RPFNA). It is not known whether there is a correlation between mammographic density and Ki-67 expression in benign breast ductal cells obtained by RPFNA.METHODS:Included in the study were 344 women at high risk for developing breast cancer (based on personal or family history), seen at The University of Kansas Medical Center high-risk breast clinic, who underwent RPFNA with cytomorphology and Ki-67 assessment plus a mammogram. Mammographic breast density was assessed using the Cumulus program. Categorical variables were analyzed by ?2 test, and continuous variables were analyzed by nonparametric test and linear regression.RESULTS:Forty-seven per cent of women were premenopausal and 53% were postmenopausal. The median age was 48 years, median 5-year Gail Risk was 2.2%, and median Ki-67 was 1.9%. The median mammographic breast density was 37%. Ki-67 expression increased with cytologic abnormality (atypia versus no atypia; P = 0.001) and younger age (=50 years versus >50 years; P = 0.001). Mammographic density was higher in premenopausal women (P = 0.001), those with lower body mass index (P < 0.001), and those with lower 5-year Gail risk (P = 0.001). Mammographic density exhibited no correlation with Ki-67 expression or cytomorphology.CONCLUSION:Given the lack of correlation of mammographic breast density with either cytomorphology or Ki-67 expression in RPFNA specimens, mammographic density and Ki-67 expression should be considered as potentially complementary response biomarkers in breast cancer chemoprevention trials

Relationship between human tumour angiogenic profile and combretastatin-induced vascular shutdown: an exploratory study

Combretastatin-A4-phosphate (CA4P) acts most effectively against immature tumour vasculature. We investigated whether histological angiogenic profile can explain the differential sensitivity of human tumours to CA4P, by correlating the kinetic changes demonstrated by dynamic MRI (DCE-MRI) in response to CA4P, with tumour immunohistochemical angiogenic markers. Tissue was received from 24 patients (mean age 59, range 32–73, 18 women, 6 men). An angiogenic profile was performed using standard immunohistochemical techniques. Dynamic MRI data were obtained for the same patients before and 4 h after CA4P. Three patients showed a statistically significant fall in Ktrans following CA4P, and one a statistically significant fall in IAUGC60. No statistically significant correlations were seen between the continuous or categorical variables and the DCE-MRI kinetic parameters other than between ang-2 and Ktrans (P=0.044). In conclusion, we found no strong relationships between changes in DCE-MRI kinetic variables following CA4P and the immunohistochemical angiogenic profile

Pathological and Biological Differences Between Screen-Detected and Interval Ductal Carcinoma in situ of the Breast

Background: The incidence of ductal carcinoma in situ (DCIS) has risen dramatically with the introduction of screening mammography. The aim was to evaluate differences in pathological and biological characteristics between patients with screen-detected and interval DCIS. Methods: From January 1992 to December 2001, 128 consecutive patients had been treated for pure DCIS at our institute. From these, 102 had been attending the Dutch breast cancer screening program. Sufficient paraffin-embedded tissue was available in 74 out of the 102 cases to evaluate biological marker expression (Her2/neu, ER, PR, p53 and cyclin D1) on tissue microarrays (TMA group). Differences in clinicopathological characteristics and marker expression between screen-detected and interval patients were evaluated. Screen-detected DCIS was classified as DCIS detected by screening mammography, when the two-year earlier examination failed to reveal an abnormality. Interval patients were classified as patients with DCIS detected within the two-year interval between two subsequent screening rounds. Results: Screen-detected DCIS was related with linear branching and coarse granular microcalcifications on mammography (p < .001) and with high-grade DCIS according to the Van Nuys classification (p = .025). In univariate analysis, screen-detected DCIS was related with Her2/neu overexpression (odds ratio [OR] = 6.5; 95%CI 1.3-31.0; p = .020), and interval DCIS was associated with low-grade (Van Nuys, OR = 7.3; 95% CI 1.6-33.3; p = .010) and PR positivity (OR = 0.3; 95%CI 0.1-1.0; p = .042). The multivariate analysis displayed an independent relation of Her2/neu overexpression with screen-detected DCIS (OR = 12.8; 95%CI 1.6-104.0; p = .018). Conclusions: These findings suggest that screen-detected DCIS is biologically more aggressive than interval DCIS and should not be regarded as overdiagnosis