Identification of biomarkers in ductal carcinoma in situ of the breast with microinvasion

<p>Abstract</p> <p>Background</p> <p>Widespread use of mammography in breast cancer screening has led to the identification of increasing numbers of patients with ductal carcinoma <it>in situ </it>(DCIS). DCIS of the breast with an area of focal invasion 1 mm or less in diameter is defined as DCIS with microinvasion, DCIS-Mi. Identification of biological differences between DCIS and DCIS-Mi may aid in understanding of the nature and causes of the progression of DCIS to invasiveness.</p> <p>Methods</p> <p>In this study, using resected breast cancer tissues, we compared pure DCIS (52 cases) and DCIS-Mi (28 cases) with regard to pathological findings of intraductal lesions, biological factors, apoptosis-related protein expression, and proliferative capacity through the use of immunohistochemistry and the TdT-mediated dUTP-biotin nick end labeling (TUNEL) method.</p> <p>Results</p> <p>There were no differences in biological factors between DCIS and DCIS-Mi, with respect to levels of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor type 2. The frequency of necrosis and positive expression ratio of survivin and Bax were significantly higher in DCIS-Mi than in DCIS. In addition, apoptotic index, Ki-67 index, and positive Bcl-2 immunolabeling tended to be higher in DCIS-Mi than in DCIS. Multivariate analysis revealed that the presence of necrosis and positive survivin expression were independent factors associated with invasion.</p> <p>Conclusion</p> <p>Compared with DCIS, DCIS-Mi is characterized by a slightly elevated cell proliferation capacity and enhanced apoptosis within the intraductal lesion, both of which are thought to promote the formation of cell necrotic foci. Furthermore, the differential expression of survivin may serve in deciding the response to therapy and may have some prognostic significance.</p

Schwann-Spheres Derived from Injured Peripheral Nerves in Adult Mice - Their In Vitro Characterization and Therapeutic Potential

Multipotent somatic stem cells have been identified in various adult tissues. However, the stem/progenitor cells of the peripheral nerves have been isolated only from fetal tissues. Here, we isolated Schwann-cell precursors/immature Schwann cells from the injured peripheral nerves of adult mice using a floating culture technique that we call “Schwann-spheres." The Schwann-spheres were derived from de-differentiated mature Schwann cells harvested 24 hours to 6 weeks after peripheral nerve injury. They had extensive self-renewal and differentiation capabilities. They strongly expressed the immature-Schwann-cell marker p75, and differentiated only into the Schwann-cell lineage. The spheres showed enhanced myelin formation and neurite growth compared to mature Schwann cells in vitro. Mature Schwann cells have been considered a promising candidate for cell-transplantation therapies to repair the damaged nervous system, whereas these “Schwann-spheres" would provide a more potential autologous cell source for such transplantation

Thermal melanism explains macroevolutionary variation of dorsal pigmentation in Eurasian vipers.

Colouration may endorse thermoregulatory and antipredatory functions in snakes. The thermal melanism hypothesis predicts that dark-coloured individuals are ecologically favoured in cool climates. However, the loss of aposematic and cryptic colourations may imply high predation for melanistic snakes. Here, we used the monophyletic group of Eurasian vipers (subfamily Viperinae) to test whether an increase in the extent of dark area inside the characteristic zigzag dorsal pattern is associated to colder environments. We measured two colouration traits in zigzag-patterned individuals (number of dorsal marks and weighted pigmentation index) and used a phylogenetic comparative approach to explore macroevolutionary patterns of dorsal pigmentation and test whether its extent is associated to ecogeographic characteristics of lineages' ranges. Phylogeneticallynaïve and phylogenetically-informed analyses yielded a signifcant association between the degree of pigmentation of the zigzag pattern and environmental variables such as solar radiation, elevation and latitude. The degree of pigmentation of the zigzag pattern is highlighted as an adaptive trait that matches range attributes mirroring cold environments irrespective of the phylogeny. These results constitute the frst large-scale evidence supporting the thermal melanism hypothesis in snakes, opening new avenues of inquiry for the mechanisms that shape the evolution of colour phenotypes

Sampling schemes and drift can bias admixture proportions inferred by structure

International audienceThe interbreeding of individuals coming from genetically differentiated but incompletely isolated populations can lead to the formation of admixed populations, having important implications in ecology and evolution. In this simulation study, we evaluate how individual admixture proportions estimated by the software structure are quantitatively affected by different factors. Using various scenarios of admixture between two diverging populations, we found that unbalanced sampling from parental populations may seriously bias the inferred admixture proportions; moreover, proportionally large samples from the admixed population can also decrease the accuracy and precision of the inferences. As expected, weak differentiation between parental populations and drift after the admixture event strongly increase the biases caused by uneven sampling. We also show that admixture proportions are generally more biased when parental populations unequally contributed to the admixed population. Finally, with few exceptions, using a large number of markers reduces those biases, but using alternative priors for individual ancestry or the uncorrelated allele model only marginally affect the inference of admixture in most situations. We conclude that unbalanced sampling may cause important biases in the admixture proportions estimated by structure, especially when a small number of markers are used, and those biases can be worsened by the effect of drift and unequal genetic contribution of parental populations. Empirical studies should thus be careful with their sampling design and consider historical characteristics when using this software to estimate the ancestry of individuals from admixed populations