| 1. |
- Garcia-Closas, Montserrat, et al.
(author)
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Heterogeneity of breast cancer associations with five susceptibility loci by clinical and pathological characteristics
- 2008
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In: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 4:4, s. e1000054-
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Journal article (peer-reviewed)abstract
- A three-stage genome-wide association study recently identified single nucleotide polymorphisms (SNPs) in five loci (fibroblast growth receptor 2 (FGFR2), trinucleotide repeat containing 9 (TNRC9), mitogen-activated protein kinase 3 K1 (MAP3K1), 8q24, and lymphocyte-specific protein 1 (LSP1)) associated with breast cancer risk. We investigated whether the associations between these SNPs and breast cancer risk varied by clinically important tumor characteristics in up to 23,039 invasive breast cancer cases and 26,273 controls from 20 studies. We also evaluated their influence on overall survival in 13,527 cases from 13 studies. All participants were of European or Asian origin. rs2981582 in FGFR2 was more strongly related to ER-positive (per-allele OR (95%CI) = 1.31 (1.27-1.36)) than ER-negative (1.08 (1.03-1.14)) disease (P for heterogeneity = 10(-13)). This SNP was also more strongly related to PR-positive, low grade and node positive tumors (P = 10(-5), 10(-8), 0.013, respectively). The association for rs13281615 in 8q24 was stronger for ER-positive, PR-positive, and low grade tumors (P = 0.001, 0.011 and 10(-4), respectively). The differences in the associations between SNPs in FGFR2 and 8q24 and risk by ER and grade remained significant after permutation adjustment for multiple comparisons and after adjustment for other tumor characteristics. Three SNPs (rs2981582, rs3803662, and rs889312) showed weak but significant associations with ER-negative disease, the strongest association being for rs3803662 in TNRC9 (1.14 (1.09-1.21)). rs13281615 in 8q24 was associated with an improvement in survival after diagnosis (per-allele HR = 0.90 (0.83-0.97). The association was attenuated and non-significant after adjusting for known prognostic factors. Our findings show that common genetic variants influence the pathological subtype of breast cancer and provide further support for the hypothesis that ER-positive and ER-negative disease are biologically distinct. Understanding the etiologic heterogeneity of breast cancer may ultimately result in improvements in prevention, early detection, and treatment.
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| 2. |
- Janzen, Viktor, et al.
(author)
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Hematopoietic stem cell responsiveness to exogenous signals is limited by Caspase-3
- 2008
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In: Cell Stem Cell. - : Elsevier BV. - 1934-5909. ; 2:6, s. 584-594
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Journal article (peer-reviewed)abstract
- Limited responsiveness to inflammatory cytokines is a feature of adult hematopoietic stem cells and contributes to the relative quiescence and durability of the stem cell population in vivo. Here we report that the executioner Caspase, Caspase-3, unexpectedly participates in that process. Mice deficient in Caspase-3 had increased numbers of immunophenotypic long-term repopulating stem cells in association with multiple functional changes, most prominently cell cycling. Though these changes were cell autonomous, they reflected altered activation by exogenous signals. Caspase-3(-/-) cells exhibited cell type-specific changes in phosphorylated members of the Ras-Raf-MEK-ERK pathway in response to specific cytokines, while notably, members of other pathways, such as pSTAT3, pSTAT5, pAKT, pp38 MAPK, pSmad2, and pSmad3, were unaffected. Caspase-3 contributes to stem cell quiescence, dampening specific signaling events and thereby cell responsiveness to microenvironmental stimuli.
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| 3. |
- Stritzinger, Maximilian, et al.
(author)
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The He-Rich Core-Collapse Supernova 2007Y : Observations from X-Ray to Radio Wavelengths
- 2009
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In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 696:1, s. 713-728
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Journal article (peer-reviewed)abstract
- A detailed study spanning approximately a year has been conducted on the Type Ib supernova (SN) 2007Y. Imaging was obtained from X-ray to radio wavelengths, and a comprehensive set of multi-band (w2m2w1u'g'r'i'UBVYJHKs ) light curves and optical spectroscopy is presented. A virtually complete bolometric light curve is derived, from which we infer a 56Ni mass of 0.06 M sun. The early spectrum strongly resembles SN 2005bf and exhibits high-velocity features of Ca II and Hα during late epochs the spectrum shows evidence of an ejecta-wind interaction. Nebular emission lines have similar widths and exhibit profiles that indicate a lack of major asymmetry in the ejecta. Late phase spectra are modeled with a non-LTE code, from which we find 56Ni, O, and total-ejecta masses (excluding He) to be 0.06, 0.2, and 0.42 M sun, respectively, below 4500 km s-1. The 56Ni mass confirms results obtained from the bolometric light curve. The oxygen abundance suggests that the progenitor was most likely a ≈3.3 M sun He core star that evolved from a zero-age-main-sequence mass of 10-13 M sun. The explosion energy is determined to be ≈1050 erg, and the mass-loss rate of the progenitor is constrained from X-ray and radio observations to be lsim10-6 M sun yr-1. SN 2007Y is among the least energetic normal Type Ib SNe ever studied. Partly based on observations collected at the European Southern Observatory, La Silla and Paranal Observatories, Chile (ESO Programme 078.D-0048 and 380.D-0272).
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