23 research outputs found

    Biomarker phenotyping drives clinical management in axillary sentinel node: A retrospective study on women with primary breast cancer in 2002

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    The current study examined if cancer biomarker phenotyping could predict the clinical/pathological status of axillary nodes in women with primary breast cancer. Primary breast cancers from 2002 were analyzed for tumor size, estrogen receptor (ER), progesterone receptor (PgR), Ki.67MIB expression and Her2/neu amplification. Relationships between the clinical and pathological status of the axilla and the biological subtypes classification were analyzed using univariate, multivariate and regression tree analysis. A total of 65% of women with axillary nodes clinically involved had complete axillary node dissection (ALND) while 705 women with clinically negative axillary underwent sentinel lymph node biopsy (SLNB), 18.5% of the latter had at least one pathologically SLNB involved node. Multivariate analysis revealed that the Luminal A subtype was significantly associated (OR 0.62; P<10-9) with clinical negative axilla while HER2pos/not Luminal was associated with clinical positivity (OR 1.71; P<0.01). No significant association between biological subtypes and SLNB status was demonstrated. Regression tree analysis revealed that subgroups with significantly different probability of SLNB status were separated according to tumor size and PgR values. In conclusion, the current study demonstrated that biomarker breast cancer phenotyping is significantly associated with clinical status of axillary nodes but not with pathological involvement of nodes at SLNB. Regression tree analysis could represent a valid attempt to individualize some patients subgroups candidate to different surgical axilla approaches

    EXPLORING ANTICORRELATIONS AND LIGHT ELEMENT VARIATIONS IN NORTHERN GLOBULAR CLUSTERS OBSERVED BY THE APOGEE SURVEY

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    We investigate the light-element behavior of red giant stars in northern globular clusters (GCs) observed by the SDSS-III Apache Point Observatory Galactic Evolution Experiment. We derive abundances of 9 elements (Fe, C, N, O, Mg, Al, Si, Ca, and Ti) for 428 red giant stars in 10 GCs. The intrinsic abundance range relative to measurement errors is examined, and the well-known C–N and Mg–Al anticorrelations are explored using an extreme-deconvolution code for the first time in a consistent way. We find that Mg and Al drive the population membership in most clusters, except in M107 and M71, the two most metal-rich clusters in our study, where the grouping is most sensitive to N. We also find a diversity in the abundance distributions, with some clusters exhibiting clear abundance bimodalities (for example M3 and M53) while others show extended distributions. The spread of Al abundances increases significantly as cluster average metallicity decreases as previously found by other works, which we take as evidence that low metallicity, intermediate mass AGB polluters were more common in the more metal-poor clusters. The statistically significant correlation of [Al/Fe] with [Si/Fe] in M15 suggests that 28Si leakage has occurred in this cluster. We also present C, N, and O abundances for stars cooler than 4500 K and examine the behavior of A(C+N+O) in each cluster as a function of temperature and [Al/Fe]. The scatter of A(C+N +O) is close to its estimated uncertainty in all clusters and independent of stellar temperature. A(C+N+O) exhibits small correlations and anticorrelations with [Al/Fe] in M3 and M13, but we cannot be certain about these relations given the size of our abundance uncertainties. Star-to-star variations of a-element (Si, Ca, Ti) abundances are comparable to our estimated errors in all clusters

    Pulsating White Dwarf Stars and Precision Asteroseismology

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    Galactic history is written in the white dwarf stars. Their surface properties hint at interiors composed of matter under extreme conditions. In the forty years since their discovery, pulsating white dwarf stars have moved from side-show curiosities to center stage as important tools for unraveling the deep mysteries of the Universe. Innovative observational techniques and theoretical modeling tools have breathed life into precision asteroseismology. We are just learning to use this powerful tool, confronting theoretical models with observed frequencies and their time rate-of-change. With this tool, we calibrate white dwarf cosmochronology; we explore equations of state; we measure stellar masses, rotation rates, and nuclear reaction rates; we explore the physics of interior crystallization; we study the structure of the progenitors of Type Ia supernovae, and we test models of dark matter. The white dwarf pulsations are at once the heartbeat of galactic history and a window into unexplored and exotic physics.Comment: 70 pages, 11 figures, to be published in Annual Review of Astronomy and Astrophysics 200

    Regulated expression of matrix metalloproteinases, inflammatory mediators, and endometrial matrix remodeling by 17beta-estradiol in the immature rat uterus

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    <p>Abstract</p> <p>Background</p> <p>Administration of a single physiological dose of 17beta-estradiol (E2:40 microg/kg) to the ovariectomized immature rat rapidly induces uterine growth and remodeling. The response is characterized by changes in endometrial stromal architecture during an inflammatory-like response that likely involves activated matrix-metalloproteinases (MMPs). While estrogen is known as an inducer of endometrial growth, its role in specific expression of MMP family members in vivo is poorly characterized. E2-induced changes in MMP-2, -3, -7, and -9 mRNA and protein expression were analyzed to survey regulation along an extended time course 0-72 hours post-treatment. Because E2 effects inflammatory-like changes that may alter MMP expression, we assessed changes in tissue levels of TNF-alpha and MCP-1, and we utilized dexamethasone (600 microg/kg) to better understand the role of inflammation on matrix remodeling.</p> <p>Methods</p> <p>Ovariectomized 21 day-old female Sprague-Dawley rats were administered E2 and uterine tissues were extracted and prepared for transmission electron microscopy (TEM), mRNA extraction and real-time RT-PCR, protein extraction and Western blot, or gelatin zymography. In inhibitor studies, pretreatment compounds were administered prior to E2 and tissues were harvested at 4 hours post-hormone challenge.</p> <p>Results</p> <p>Using a novel TEM method to quantitatively assess changes in stromal collagen density, we show that E2-induced matrix remodeling is rapid in onset (< 1 hour) and leads to a 70% reduction in collagen density by 4 hours. Matrix remodeling is MMP-dependent, as pretreatment with batimastat ablates the hormone effect. MMP-3, -7, and -9 and inflammatory markers (TNF-alpha and MCP-1) are transiently upregulated with peak expression at 4 hours post-E2 treatment. MMP-2 expression is increased by E2 but highest expression and activity occur later in the response (48 hours). Dexamethasone inhibits E2-modulated changes in collagen density and expression of MMPs although these effects are variable. Dexamethasone upregulates MMP-3 mRNA but not protein levels, inhibiting E2-induced upregulation of MMP-7, and -9, and MCP-1 mRNA and protein but not inhibiting the hormone-induced increase in TNF-alpha mRNA.</p> <p>Conclusion</p> <p>The data demonstrate that E2-regulated endometrial remodeling is rapid in onset (<1 hour) and peak expression of MMPs and inflammatory mediators correlates temporally with the period of lowest stromal collagen density during uterine tissue hypertrophy.</p

    Contractile properties of different types of dog muscle fibres.

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    In this work we studied the functional properties of canine myosin isoforms in skeletal and specialized muscles of the dog such as semimembranosus, vastus lateralis, lungissimus dorsi, diaphragm and thyroarytenoideus. We determined the isometric tension (Po), maximum shortening velocity (Vo) of single fibres and the speed (Vf) of actin filament sliding on myosin extracted from single muscle fibres in an in vitro motility assay (IVMA). Single fibres were identified on the basis of their myosin isoform composition, determined by gel electrophoresis. The results obtained showed the progressive increase of Vo in the order 1/slow<2A<2X<2B thus confirming the identification of the myosin isoforms carried out on the basis of their primary structure. Furthermore, the results indicated a close proportionality between Vo and Vf, thus suggesting that the diversity in Vo can be attributed to the different myosin isoform composition
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