Correspondence Between Simple 3-D MRI-Based Computer Models and In-Vivo EP Measurements in Swine With Chronic Infarctions

International audienceThe aim of this paper was to compare several in-vivo electrophysiological (EP) characteristics measured in a swine model of chronic infarct, with those predicted by simple 3-D MRI-based computer models built from ex-vivo scans (voxel size <1mm3 ). Specifically, we recorded electroanatomical voltage maps (EAVM) in six animals, and ECG waves during induction of arrhythmia in two of these cases. The infarct heterogeneities (dense scar and border zone) as well as fiber directions were estimated using diffusion weighted DW-MRI.We found a good correspondence (r = 0.9) between scar areas delineated on the EAVM and MRI maps. For theoretical predictions, we used a simple two-variable macroscopic model and computed the propagation of action potential after application of a train of stimuli, with location and timing replicating the stimulation protocol used in the in-vivo EP study. Simulation results are exemplified for two hearts: one with noninducible ventricular tachycardia (VT), and another with a macroreentrant VT (for the latter, the average predicted VT cycle length was 273 ms, compared to a recorded VT of 250 ms)

Epigenetic reprogramming of breast cancer cells with oocyte extracts

<p>Abstract</p> <p>Background</p> <p>Breast cancer is a disease characterised by both genetic and epigenetic alterations. Epigenetic silencing of tumour suppressor genes is an early event in breast carcinogenesis and reversion of gene silencing by epigenetic reprogramming can provide clues to the mechanisms responsible for tumour initiation and progression. In this study we apply the reprogramming capacity of oocytes to cancer cells in order to study breast oncogenesis.</p> <p>Results</p> <p>We show that breast cancer cells can be directly reprogrammed by amphibian oocyte extracts. The reprogramming effect, after six hours of treatment, in the absence of DNA replication, includes DNA demethylation and removal of repressive histone marks at the promoters of tumour suppressor genes; also, expression of the silenced genes is re-activated in response to treatment. This activity is specific to oocytes as it is not elicited by extracts from ovulated eggs, and is present at very limited levels in extracts from mouse embryonic stem cells. Epigenetic reprogramming in oocyte extracts results in reduction of cancer cell growth under anchorage independent conditions and a reduction in tumour growth in mouse xenografts.</p> <p>Conclusions</p> <p>This study presents a new method to investigate tumour reversion by epigenetic reprogramming. After testing extracts from different sources, we found that axolotl oocyte extracts possess superior reprogramming ability, which reverses epigenetic silencing of tumour suppressor genes and tumorigenicity of breast cancer cells in a mouse xenograft model. Therefore this system can be extremely valuable for dissecting the mechanisms involved in tumour suppressor gene silencing and identifying molecular activities capable of arresting tumour growth. These applications can ultimately shed light on the contribution of epigenetic alterations in breast cancer and advance the development of epigenetic therapies.</p

Treatment of Adrenocorticotropin-Dependent Cushing’s Syndrome: A Consensus Statement

Objective: Our objective was to evaluate the published literature and reach a consensus on the treatment of patients with ACTH-dependent Cushing’s syndrome, because there is no recent consensus on the management of this rare disorder