The normal breast microenvironment of premenopausal women differentially influences the behavior of breast cancer cells in vitro and in vivo

<p>Abstract</p> <p>Background</p> <p>Breast cancer studies frequently focus on the role of the tumor microenvironment in the promotion of cancer; however, the influence of the normal breast microenvironment on cancer cells remains relatively unknown. To investigate the role of the normal breast microenvironment on breast cancer cell tumorigenicity, we examined whether extracellular matrix molecules (ECM) derived from premenopausal African-American (AA) or Caucasian-American (CAU) breast tissue would affect the tumorigenicity of cancer cells <it>in vitro </it>and <it>in vivo</it>. We chose these two populations because of the well documented predisposition of AA women to develop aggressive, highly metastatic breast cancer compared to CAU women.</p> <p>Methods</p> <p>The effects of primary breast fibroblasts on tumorigenicity were analyzed via real-time PCR arrays and mouse xenograft models. Whole breast ECM was isolated, analyzed via zymography, and its effects on breast cancer cell aggressiveness were tested <it>in vitro </it>via soft agar and invasion assays, and <it>in vivo </it>via xenograft models. Breast ECM and hormone metabolites were analyzed via mass spectrometry.</p> <p>Results</p> <p>Mouse mammary glands humanized with premenopausal CAU fibroblasts and injected with primary breast cancer cells developed significantly larger tumors compared to AA humanized glands. Examination of 164 ECM molecules and cytokines from CAU-derived fibroblasts demonstrated a differentially regulated set of ECM proteins and increased cytokine expression. Whole breast ECM was isolated; invasion and soft agar assays demonstrated that estrogen receptor (ER)^-, progesterone receptor (PR)/PR^-cells were significantly more aggressive when in contact with AA ECM, as were ER⁺/PR⁺cells with CAU ECM. Using zymography, protease activity was comparatively upregulated in CAU ECM. In xenograft models, CAU ECM significantly increased the tumorigenicity of ER⁺/PR⁺cells and enhanced metastases. Mass spectrometry analysis of ECM proteins showed that only 1,759 of approximately 8,000 identified were in common. In the AA dataset, proteins associated with breast cancer were primarily related to tumorigenesis/neoplasia, while CAU unique proteins were involved with growth/metastasis. Using a novel mass spectrometry method, 17 biologically active hormones were measured; estradiol, estriol and 2-methoxyestrone were significantly higher in CAU breast tissue.</p> <p>Conclusions</p> <p>This study details normal premenopausal breast tissue composition, delineates potential mechanisms for breast cancer development, and provides data for further investigation into the role of the microenvironment in cancer disparities.</p

A decentralized control mechanism for stream processing networks

Data streaming applications are becoming more and more common due to the rapid development in emerging areas such as sensor networks, multimedia streaming, and on-line data mining, etc. These applications are often running in a decentralized, distributed environment. The requirements for processing large volumes of streaming data at real time have posed many great design challenges. One of the critical issues is to optimize the ongoing resource consumption of multiple, distributed, cooperating processing units. In this paper, we consider a generic model for the general stream data processing systems. We address the resource allocation problem for a collection of processing units so as to maximize the weighted sum of the throughput of different streams. Each processing unit may require multiple input data streams simultaneously and produce one or many valuable output streams. We develop decentralized control mechanisms that maximize the overall system throughput in such data stream processing networks. Performance analysis on the optimality and complexity of these mechanisms are also provided

Evaluation of the Diagnostic Efficacy of Xpert CT/NG for Chlamydia trachomatis and Neisseria gonorrhoeae

Background. Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are widely spread across the world. Asymptomatic or inconspicuous CT/NG infections are difficult to diagnose and treat. Traditional methods have the disadvantages of low detection rate, inaccurate results, and long detection time. However, Xpert CT/NG makes up for the aforementioned shortcomings and has research value and popularization significance. Methods. PubMed, Embase, Cochrane Library, and Web of Science were systematically searched, and studies were screened using Xpert CT/NG for diagnosing CT/NG. QUADAS-2 was used to evaluate the quality of the eligible studies. Then, two groups of researchers independently extracted data from these studies. Meta-analyses of sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and the area under the curve (AUC) of the summary receiver operating characteristic (SROC) curve were conducted using Meta-DiSc 1.4. Finally, Deek’s funnel plots were made using Stata 12.0 to evaluate publication bias. Results. 14 studies were identified, and 46 fourfold tables were extracted in this meta-analysis. The pooled SEN, SPE, PLR, NLR, DOR, and AUC in diagnosing CT were 0.94 (95% confidence interval (CI): 0.93–0.95), 0.99 (95% CI: 0.99–1.00), 97.17 (95% CI: 56.76–166.32), 0.07 (95% CI: 0.04–0.12), 1857.25 (95% CI: 943.78–3654.86), and 0.9960, respectively. The pooled SEN, SPE, PLR, NLR, DOR, and AUC in diagnosing NG were 0.95 (95% CI: 0.93–0.96), 1.00 (95% CI: 1.00–1.00), 278.15 (95% CI: 152.41–507.63), 0.08 (95% CI: 0.06–0.12), 4290.70 (95% CI: 2161.78–8516.16), and 0.9980, respectively. Conclusions. Xpert CT/NG had high diagnostic sensitivity and specificity for CT and NG. However, more evidence is required to confirm that Xpert CT/NG might serve as the primary method for detecting CT and NG and even the gold standard for diagnosis in the future

Metasomatized lithosphere–asthenosphere interaction during slab roll-back: Evidence from Late Carboniferous gabbros in the Luotuogou area, Central Tianshan

Late Carboniferous igneous rocks are widespread in the western Tianshan, but the tectonic settings for these rocks remain controversial. We report a plagioclase 40Ar/39Ar age, and geochemical, Sr–Nd isotope and LA–ICPMS clinopyroxene trace element data for gabbros in the Luotuogou region. The tholeiitic Luotuogou gabbros give a Late Carboniferous (312 ± 1 Ma) 40Ar/39Ar age and are characterized by high and variable εNd(t) values ranging from + 3.7 to + 7.8. They have geochemical features of both intra-plate and island arc magmatic rocks, i.e., relatively high TiO2 (0.6–2.2 wt.%), Nb (4.2–24 ppm) and Zr (51.4–283 ppm) contents combined with variable and slightly high Nb/La ratios (0.24–1.8, mostly > 0.7), and negative to positive Nb anomalies. The gabbros contain zoned clinopyroxenes, with Mg- and Cr-rich cores. Their parental magmas, as calculated using trace element data from Cr-rich (> 3000 ppm) clinopyroxene cores and clinopyroxene/basaltic liquid partition coefficients, show enrichments in incompatible elements, and prominent negative to slightly positive Nb anomalies, indicative of the influence of subduction-related compositions in their mantle source. These features indicate that the Luotuogou gabbros were most likely formed by interactions between asthenospheric and metasomatized lithospheric mantle. They were most plausibly formed by mixing between the asthenospheric mantle-derived and metasomatized lithosphere mantle-derived melts. Mixing was the result of asthenosphere upwelling triggered by roll-back of the subducted Paleo-Junggar Oceanic Plate rather than mantle plume-related rifting or post-collisional break-off during the Late Carboniferous