Extremely low tau (< 2 dyne/cm(2)) stimulates high rates of smooth muscle cellular proliferation in arterialized vein patches. NIT is accelerated in these regions of low tau far beyond that predicted by a simple linear model. The nonlinear nature of the cellular proliferative response and NIT at tau less than 2 dyne/cm(2) may explain the rapid progression of neointimal lesions in failing bypass grafts.

Injury caused by distention of the arterial wall by balloon angioplasty can result in apoptosis and vascular smooth muscle cell proliferation. Here, we report that a brief exposure of the arterial lumen to a genetically engineered, attenuated herpes simplex virus 1 blocks activation of caspase 3-dependent apoptosis and MAPKdependent cell proliferation induced by carotid artery balloon angioplasty and ligation to reduce blood flow. The procedure enables the restoration of the endothelial cell layer lining the lumen and prevents neointimal hyperplasia and restenosis. These findings have a broad application in prevention of balloon angioplasty-induced restenosis.neointimal hyperplasia ͉ restenosis ͉ vascular smooth muscle cells ͉ endothelial cells

Background-Arterial remodeling occurs as a response to hemodynamic change and direct vessel wall injury through the process of neointimal hyperplasia (NH). A concomitant response of vascular smooth muscle cell (VSMC) proliferation and apoptosis exists. The purpose of this study is to assess the cellular response of vessels following exposure to low shear stress (τ) and balloon injury in order to further elucidate the mechanisms underlying vascular injury. Our hypothesis is that the combination of low τ and balloon injury results in NH approximating that seen in clinical arterial restenosis, and that quantitative analysis of VSMC proliferation and apoptosis correlates with the associated increase in arterial remodeling.

IntroductionPrevious work from this laboratory demonstrated that magnetic resonance imaging (MRI) detects early murine mammary cancers and reliably differentiates between in situ and invasive cancer. Based on this previous work, we used MRI to study initiation and progression of murine mammary cancer, and monitor the transition from the in situ to the invasive phase.MethodsIn total, seven female C3(1) SV40 Tag mice were imaged every two weeks between the ages of 8 to 23 weeks. Lesions were identified on T2-weighted images acquired at 9.4 Tesla based on their morphology and growth rates. Lesions were traced manually on MR images of each slice. Volume of each lesion was calculated by adding measurements from individual slices. Plots of lesion volume versus time were analyzed to obtain the specific growth rate (SGR). The time at which in situ cancers (referred to as ‘mammary intraepithelial neoplasia (MIN)’) and invasive cancers were first detected; and the time at which in situ cancers became invasive were recorded.ResultsA total of 121 cancers (14 to 25 per mouse) were identified in seven mice. On average the MIN lesions and invasive cancers were first detected when mice were 13 and 18 weeks old, respectively. The average SGR was 0.47 ± 0.18 week-1 and there were no differences (P >0.05) between mice. 74 lesions had significantly different tumor growth rates before and after ~17 weeks of age; with average doubling times (DT) of 1.88 and 1.27 weeks, respectively. The average DT was significantly shorter (P <0.0001) after 17 weeks of age. However, the DT for some cancers was longer after 17 weeks of age, and about 10% of the cancers detected did not progress to the invasive stage.ConclusionsA wide range of growth rates were observed in SV40 mammary cancers. Most cancers transitioned to a more aggressive phenotype at approximately 17 weeks of age, but some cancers became less aggressive. The results suggest that the biology of mammary cancers is extremely heterogeneous. This work is a first step towards use of MRI to improve understanding of factors that control and/or signal the development of aggressive breast cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-014-0495-6) contains supplementary material, which is available to authorized users.

Purpose: This study investigates the feasibility of T 2 * to be a diagnostic indicator of early breast cancer in a mouse model. T 2 * is sensitive to susceptibility effects due to local inhomogeneity of the magnetic field, e.g., caused by hemosiderin or deoxyhemoglobin. In these mouse models, unlike in patients, the characteristics of single mammary ducts containing pure intraductal cancer can be evaluated. Methods: The C3(1)SV40Tag mouse model of breast cancer (n ¼ 11) and normal FVB=N mice (n ¼ 6) were used to measure T 2 * of normal mammary gland tissue, intraepithelial neoplasia, invasive cancers, mammary lymph nodes, and muscle. MRI experiments were performed on a 9.4T animal scanner. High resolution (117 microns) axial 2D multislice gradient echo images with fat suppression were acquired first to identify inguinal mammary gland. Then a multislice multigradient echo pulse sequence with and without fat suppression were performed over the inguinal mammary gland. The modulus of a complex double exponential decay detected by the multigradient echo sequence was used to fit the absolute proton free induction decay averaged over a region of interest to determine the T 2 * of water and fat signals. Results: The measured T 2 * values of tumor and muscle are similar ($15 ms), and almost twice that of lymph nodes ($8 ms). There was a statistically significant difference (p < 0.03) between T 2 * in normal mammary tissue (13.7 6 2.9 ms) and intraductal cancers (11 6 2.0 ms) when a fat suppression pulse was applied. Conclusions: These are the first reported T 2 * measurements from single mammary ducts. The results demonstrated that T 2 * measurements may have utility for identifying early pre-invasive cancers in mouse models. This may inspire similar research for patients using T 2 * for diagnostic imaging of early breast cancer.