Tamoxifen and Flaxseed Alter Angiogenesis Regulators in Normal Human Breast Tissue In Vivo

The incidence of breast cancer is increasing in the Western world and there is an urgent need for studies of the mechanisms of sex steroids in order to develop novel preventive strategies. Diet modifications may be among the means for breast cancer prevention. Angiogenesis, key in tumor progression, is regulated by the balance between pro- and anti-angiogenic factors, which are controlled in the extracellular space. Sampling of these molecules at their bioactive compartment is therefore needed. The aims of this study were to explore if tamoxifen, one of the most used anti-estrogen treatments for breast cancer affected some of the most important endogenous angiogenesis regulators, vascular endothelial growth factor (VEGF), angiogenin, and endostatin in normal breast tissue in vivo and if a diet supplementation with flaxseed had similar effects as tamoxifen in the breast. Microdialysis was used for in situ sampling of extracellular proteins in normal breast tissue of women before and after six weeks of tamoxifen treatment or before and after addition of 25 g/day of ground flaxseed to the diet or in control women. We show significant correlations between estradiol and levels of VEGF, angiogenin, and endostatin in vivo, which was verified in ex vivo breast tissue culture. Moreover, tamoxifen decreased the levels of VEGF and angiogenin in the breast whereas endostatin increased significantly. Flaxseed did not alter VEGF or angiogenin levels but similar to tamoxifen the levels of endostatin increased significantly. We conclude that one of the mechanisms of tamoxifen in normal breast tissue include tipping of the angiogenic balance into an anti-angiogenic state and that flaxseed has limited effects on the pro-angiogenic factors whereas the anti-angiogenic endostatin may be modified by diet. Further studies of diet modifications for breast cancer prevention are warranted

Krox-20 controls SCIP expression, cell cycle exit and susceptibility to apoptosis in developing myelinating Schwann cells.

The transcription factors Krox-20 and SCIP each play important roles in the differentiation of Schwann cells. However, the genes encoding these two proteins exhibit distinct time courses of expression and yield distinct cellular phenotypes upon mutation. SCIP is expressed prior to the initial appearance of Krox-20, and is transient in both the myelinating and non-myelinating Schwann cell lineages; while in contrast, Krox-20 appears approximately 24 hours after SCIP and then only within the myelinating lineage, where its expression is stably maintained into adulthood. Similarly, differentiation of SCIP-/- Schwann cells appears to transiently stall at the promyelinating stage that precedes myelination, whereas Krox-20(-/-) cells are, by morphological criteria, arrested at this stage. These observations led us to examine SCIP regulation and Schwann cell phenotype in Krox-20 mouse mutants. We find that in Krox-20(-/-) Schwann cells, SCIP expression is converted from transient to sustained. We further observe that both Schwann cell proliferation and apoptosis, which are normal features of SCIP+ cells, are also markedly increased late in postnatal development in Krox-20 mutants relative to wild type, and that the levels of cell division and apoptosis are balanced to yield a stable number of Schwann cells within peripheral nerves. These data demonstrate that the loss of Krox-20 in myelinating Schwann cells arrests differentiation at the promyelinating stage, as assessed by SCIP expression, mitotic activity and susceptibility to apoptosis

Gene expression in inherited human craniosynostosis.

Univ Sao Paulo, BR-05508 Sao Paulo, BrazilEscola Paulista Med, BR-04023 Sao Paulo, BrazilUniv Sao Paulo, Dept Plast Surg, BR-05508 Sao Paulo, BrazilUniv Sao Paulo, Dept Neurosurg, BR-05508 Sao Paulo, BrazilEscola Paulista Med, BR-04023 Sao Paulo, BrazilWeb of Scienc

Sleep detection using physiological signals from a wearable device

Internet of things for medical devices is revolutionizing healthcare industry by providing platforms for data collection via cloud gateways and analytics. In this paper, we propose a process for developing a proof of concept solution for sleep detection by observing a set of am- bulatory physiological parameters in a completely non-invasive manner. Observing and detecting the state of sleep and also its quality, in an objective way, has been a challenging problem that impacts many medical fields. With the solution presented here, we propose to collect physiological signals from wearable devices, which in our case consists of a smart wristband equipped with sensors and a protocol for communication with a mobile device. With machine learning based algorithms, that we developed, we are able to detect sleep from wakefulness in up to 93% of cases. The results from our study are promising with a potential for novel insights and effective methods to manage sleep disturbances and improve sleep quality