High-throughput techniques have identified numerous antisense (AS) transcripts and long non-coding RNAs (ncRNAs). However, their significance in cancer biology remains largely unknown. Here, we report an androgen-responsive long ncRNA, CTBP1-AS, located in the AS region of C-terminal binding protein 1 (CTBP1), which is a corepressor for androgen receptor. CTBP1-AS is predominantly localized in the nucleus and its expression is generally upregulated in prostate cancer. CTBP1-AS promotes both hormonedependent and castration-resistant tumour growth. Mechanistically, CTBP1-AS directly represses CTBP1 expression by recruiting the RNA-binding transcriptional repressor PSF together with histone deacetylases. CTBP1-AS also exhibits global androgen-dependent functions by inhibiting tumour-suppressor genes via the PSF-dependent mechanism thus promoting cell cycle progression. Our findings provide new insights into the functions of ncRNAs that directly contribute to prostate cancer progression.

Background and Purpose-Wall shear stress (WSS) is one of the main pathogenic factors in the development of saccular cerebral aneurysms. The magnitude and distribution of the WSS in and around human middle cerebral artery (MCA) aneurysms were analyzed using the method of computed fluid dynamics (CFD). Methods-Twenty mathematical models of MCA vessels with aneurysms were created by 3-dimensional computed tomographic angiography. CFD calculations were performed by using our original finite-element solver with the assumption of Newtonian fluid property for blood and the rigid wall property for the vessel and the aneurysm. Results-The maximum WSS in the calculated region tended to occur near the neck of the aneurysm, not in its tip or bleb.The magnitude of the maximum WSS was 14.39Ϯ6.21 N/m 2 , which was 4-times higher than the average WSS in the vessel region (3.64Ϯ1.25 N/m 2 ). The average WSS of the aneurysm region (1.64Ϯ1.16 N/m 2 ) was significantly lower than that of the vessel region (PϽ0.05). The WSSs at the tip of ruptured aneurysms were markedly low. Conclusions-These results suggest that in contrast to the pathogenic effect of a high WSS in the initiating phase, a low WSS may facilitate the growing phase and may trigger the rupture of a cerebral aneurysm by causing degenerative changes in the aneurysm wall. The WSS of the aneurysm region may be of some help for the prediction of rupture.

Hemodynamic factors like the wall shear stress play an important role in cardiovascular diseases. To investigate the influence of hemodynamic factors in blood vessels, the authors have developed a numerical fluid-structure interaction (FSI) analysis technique. The objective is to use numerical simulation as an effective tool to predict phenomena in a living human body. We applied the technique to a patient-specific arterial model, and with that we showed the effect of wall deformation on the WSS distribution. In this paper, we compute the interaction between the blood flow and the arterial wall for a patient-specific cerebral aneurysm with various hemodynamic conditions, such as hypertension. We particularly focus on the effects of hypertensive blood pressure on the interaction and the WSS, because hypertension is reported to be a risk factor in rupture of aneurysms. We also aim to show the possibility of FSI computations with hemodynamic conditions representing those risk factors in cardiovascular disease. The simulations show that the transient behavior of the interaction under hypertensive blood pressure is significantly different from the interaction under normal blood pressure. The transient behavior of the blood-flow velocity, and the resulting WSS and the mechanical stress in R. Torii (B) the aneurysmal wall, are significantly affected by hypertension. The results imply that hypertension affects the growth of an aneurysm and the damage in arterial tissues.

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Fluid-structure interaction (FSI) simulations of a cerebral aneurysm with the linearly elastic and hyper-elastic wall constitutive models are carried out to investigate the influence of the wall-structure model on patient-specific FSI simulations. The maximum displacement computed with the hyper-elastic model is 36% smaller compared to the linearly elastic material model, but the displacement patterns such as the site of local maxima are not sensitive to the wall models. The blood near the apex of an aneurysm is likely to be stagnant, which causes very low wall shear stress and is a factor in rupture by degrading the aneurysmal wall. In this study, however, relatively high flow velocities due to the interaction between the blood flow and aneurysmal wall are seen to be independent of the wall model. The present results indicate that both linearly elastic and hyper-elastic models can be useful to investigate aneurysm FSI.

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Summary: We simultaneously measured neurotransmit ter amino acids by the microdialysis technique and corti cal CBP by laser-Doppler flowmetry in the ischemic pen umbral cortex of rats subjected to 2-h normothermic (36.5-37SC) transient middle cerebral artery (MCA) clip occlusion. Brains were perfusion-fixed 3 days later and infarct volume measured. CBP (% of preischemic values) fell to 32 ± 2% (mean ± SD) during ischemia and rose to 157 ± 68% during recirculation. Extracellular glutamate levels increased from a baseline value of 7 ± 3 f.LM to a peak value of 180 ± 247 f.LM 20-30 min following onset of ischemia but subsequently returned to near baseline lev els after 70 min of ischemia despite ongoing MCA occlu sion. The threshold CBP for moderate glutamate release was 48%. Massive glutamate release was seen during the first 60 min of MCA occlusion in the two animals showing Glutamate-mediated excitotoxicity, though not the sole factor, is now accepted as a major mecha nism of ischemic neuronal damage. In in vitro cell culture studies, the vulnerability of both hippocam pal and cortical neurons to anoxia has been related to glutamate release from presynaptic terminals (Rothman, 1984; Choi et aI., 1987). In in vivo stud ies of both global and focal ischemia, extracellular glutamate levels increase massively during the isch emic period (Benveniste et aI., 1984; Hagberg et aI., Abbreviations used: EI, excitotoxic index; GABA, -y-ami nobutyrate; MeA, middle cerebral artery. 575the largest infarcts and occurred at CBP values .,;20% of control levels. Mean CBP during ischemia exhibited an inverse relationship with infarct volume, and the magni tude of glutamate release during ischemia was positively correlated with infarct volume. Extracellular -y-aminobu tyrate and glycine changes were similar to those of glu tamate but showed no significant correlation with infarct volume. These results suggest that (a) accumulation of extracellular glutamate is an important determinant of in jury in the setting of reversible MCA occlusion and (b) reuptake systems for neurotransmitter amino acids may be functional in the penumbra during transient focal isch emia.