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1.
Ryan Wilcox Bryan E Welm Jeffrey T Chang Evan Johnson Avrum Spira Stefanie S Jeffrey Andrea H Bild 《Molecular systems biology》2011,7(1)
Identifying the best drug for each cancer patient requires an efficient individualized strategy. We present MATCH (M erging genomic and pharmacologic A nalyses for T herapy CH oice), an approach using public genomic resources and drug testing of fresh tumor samples to link drugs to patients. Valproic acid (VPA) is highlighted as a proof‐of‐principle. In order to predict specific tumor types with high probability of drug sensitivity, we create drug response signatures using publically available gene expression data and assess sensitivity in a data set of >40 cancer types. Next, we evaluate drug sensitivity in matched tumor and normal tissue and exclude cancer types that are no more sensitive than normal tissue. From these analyses, breast tumors are predicted to be sensitive to VPA. A meta‐analysis across breast cancer data sets shows that aggressive subtypes are most likely to be sensitive to VPA, but all subtypes have sensitive tumors. MATCH predictions correlate significantly with growth inhibition in cancer cell lines and three‐dimensional cultures of fresh tumor samples. MATCH accurately predicts reduction in tumor growth rate following VPA treatment in patient tumor xenografts. MATCH uses genomic analysis with in vitro testing of patient tumors to select optimal drug regimens before clinical trial initiation. 相似文献
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SIBYLLE STEINBEISS HOLGER BEßLER CHRISTOF ENGELS VICKY M. TEMPERTON NINA BUCHMANN CHRISTIANE ROSCHER YVONNE KREUTZIGER JUSSI BAADE MAIKE HABEKOST GERD GLEIXNER 《Global Change Biology》2008,14(12):2937-2949
Increasing atmospheric CO2 concentration and related climate change have stimulated much interest in the potential of soils to sequester carbon. In ‘The Jena Experiment’, a managed grassland experiment on a former agricultural field, we investigated the link between plant diversity and soil carbon storage. The biodiversity gradient ranged from one to 60 species belonging to four functional groups. Stratified soil samples were taken to 30 cm depth from 86 plots in 2002, 2004 and 2006, and organic carbon contents were determined. Soil organic carbon stocks in 0–30 cm decreased from 7.3 kg C m?2 in 2002 to 6.9 kg C m?2 in 2004, but had recovered to 7.8 kg C m?2 by 2006. During the first 2 years, carbon storage was limited to the top 5 cm of soil while below 10 cm depth, carbon was lost probably as short‐term effect of the land use change. After 4 years, carbon stocks significantly increased within the top 20 cm. More importantly, carbon storage significantly increased with sown species richness (log‐transformed) in all depth segments and even carbon losses were significantly smaller with higher species richness. Although increasing species diversity increased root biomass production, statistical analyses revealed that species diversity per se was more important than biomass production for changes in soil carbon. Below 20 cm depth, the presence of one functional group, tall herbs, significantly reduced carbon losses in the beginning of the experiment. Our analysis indicates that plant species richness and certain plant functional traits accelerate the build‐up of new carbon pools within 4 years. Additionally, higher plant diversity mitigated soil carbon losses in deeper horizons. This suggests that higher biodiversity might lead to higher soil carbon sequestration in the long‐term and therefore the conservation of biodiversity might play a role in greenhouse gas mitigation. 相似文献
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Ophioglossum petiolatum . Unlike Angiopteris (Marattiales), which is monoplastidic, Ophioglossum undergoes polyplastidic meiosis like members of the fern-seed plant clade. The meiotic spindle is distinctly multipolar in
origin and is consolidated into a bipolar spindle that is variously twisted and curved to accommodate the large number of
chromosomes. Although a phragmoplast forms after first meiosis, no wall is deposited. Instead, an organelle band consisting
of intermingled plastids and mitochondria is formed in the equatorial region between the dyad domains. Following second meiosis,
a complex of phragmoplasts forms among sister and non-sister nuclei. Cell plates are deposited first between sister nuclei
and then in the region of the organelle band resulting in a tetrad of spores each with a equal allotment of organelles.
Received 30 January 2001/ Accepted in revised form 24 April 2001 相似文献
4.
Sca-1(pos) cells in the mouse mammary gland represent an enriched progenitor cell population 总被引:36,自引:0,他引:36
Welm BE Tepera SB Venezia T Graubert TA Rosen JM Goodell MA 《Developmental biology》2002,245(1):42-56
Mammary epithelium can functionally regenerate upon transplantation. This renewal capacity has been classically ascribed to the function of a multipotent mammary gland stem cell population, which has been hypothesized to be a primary target in the etiology of breast cancer. Several complementary approaches were employed in this study to identify and enrich mammary epithelial cells that retain stem cell characteristics. Using long-term BrdU labeling, a population of label retaining cells (LRCs) that lack expression of differentiation markers has been identified. LRCs isolated from mammary primary cultures were enriched for stem cell antigen-1 (Sca-1) and Hoechst dye-effluxing "side population" properties. Sca-1(pos) cells in the mammary gland were localized to the luminal epithelia by using Sca-1(+/GFP) mice, were progesterone receptor-negative, and did not bind peanut lectin. Finally, the Sca-1(pos) population is enriched for functional stem/progenitor cells, as demonstrated by its increased regenerative potential compared with Sca-1(neg) cells when transplanted into the cleared mammary fat pads of host mice. 相似文献
5.
Inducible dimerization of FGFR1: development of a mouse model to analyze progressive transformation of the mammary gland 总被引:6,自引:0,他引:6
Welm BE Freeman KW Chen M Contreras A Spencer DM Rosen JM 《The Journal of cell biology》2002,157(4):703-714
To develop an inducible and progressive model of mammary gland tumorigenesis, transgenic mice were generated with a mouse mammary tumor virus-long terminal repeat-driven, conditional, fibroblast growth factor (FGF)-independent FGF receptor (FGFR)1 (iFGFR1) that can be induced to dimerize with the drug AP20187. Treatment of transgenic mice with AP20187 resulted in iFGFR1 tyrosine phosphorylation, increased proliferation, activation of mitogen-activated protein kinase and Akt, and lateral budding. Lateral buds appeared as early as 3 d after AP20187 treatment and initially consisted of bilayered epithelial cells and displayed apical and basolateral polarity appeared after 13 d of AP20187 treatment. Invasive lesions characterized by multicell-layered lateral buds, decreased myoepithelium, increased vascular branching, and loss of cell polarity were observed after 2-4 wk of treatment. These data indicate that acute iFGFR1 signaling results in increased lateral budding of the mammary ductal epithelium, and that sustained activation induces alveolar hyperplasia and invasive lesions. 相似文献
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A flux analysis of glucose metabolism in the filamentous fungus Rhizopus oryzae was achieved using a specific radioactivity curve-matching program, TFLUX. Glycolytic and tricarboxylic acid cycle intermediates labeled through the addition of extracellular [U-14C]glucose were isolated and purified for specific radioactivity determinations. This information, together with pool sizes and the rates of glucose utilization and end product production, provided input for flux maps of the metabolic network under two different experimental conditions. Based upon the flux analysis of this system, a mutant of R. oryzae with higher lactate and lower ethanol yields than the parent was sought for and found. 相似文献
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9.
Developmental biology: vasculogenesis is a wreck without RECK 总被引:17,自引:0,他引:17
The unique membrane-associated inhibitor of matrix metalloproteinases, RECK, is required for vascular maturation during embryogenesis. The phenotype of a loss of function mutation of RECK shows the importance of pericellular proteolysis in development. 相似文献
10.
While most organs undergo development in utero, the mouse mammary gland orchestrates five major developmental stages following birth: pre-puberty, puberty, pregnancy, lactation, and involution. Induced by both local and systemic factors, these five developmental stages transpire with dramatic alterations in glandular morphology and cellular function. As an experimental system, the mammary gland provides remarkable accessibility to processes regulating stem cell function, hormone response, and epithelial-stromal-extracellular matrix interactions. This review will provide a historical perspective of the unique in vitro and in vivo techniques used to study the mammary gland and how these methods have provided valuable insight into the biology of this organ. 相似文献