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  • 1
    Publication Date: 2018-06-02
    Description: Genome-wide association studies have identified more than 90 susceptibility loci for breast cancer. However, the missing heritability is evident, and the contributions of coding variants to breast cancer susceptibility have not yet been systematically evaluated. Here, we present a large-scale whole-exome association study for breast cancer consisting of 24,162 individuals (10,055 cases and 14,107 controls). In addition to replicating known susceptibility loci (e.g., ESR1, FGFR2, and TOX3), we identify two novel missense variants in C21orf58 (rs13047478, Pmeta = 4.52 × 10−8) and ZNF526 (rs3810151, Pmeta = 7.60 × 10−9) and one new noncoding variant at 7q21.11 (P 〈 5 × 10−8). C21orf58 and ZNF526 possessed functional roles in the control of breast cancer cell growth, and the two coding variants were found to be the eQTL for several nearby genes. rs13047478 was significantly (P 〈 5.00 × 10−8) associated with the expression of genes MCM3AP and YBEY in breast mammary tissues. rs3810151 was found to be significantly associated with the expression of genes PAFAH1B3 (P = 8.39 × 10−8) and CNFN (P = 3.77 × 10−4) in human blood samples. C21orf58 and ZNF526, together with these eQTL genes, were differentially expressed in breast tumors versus normal breast. Our study reveals additional loci and novel genes for genetic predisposition to breast cancer and highlights a polygenic basis of disease development.Significance: Large-scale genetic screening identifies novel missense variants and a noncoding variant as predisposing factors for breast cancer. Cancer Res; 78(11); 3087–97. ©2018 AACR.
    Print ISSN: 0008-5472
    Electronic ISSN: 1538-7445
    Topics: Medicine
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  • 2
    ISSN: 0168-9002
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Chinese Astronomy and Astrophysics 15 (1991), S. 150-156 
    ISSN: 0275-1062
    Keywords: Stars-M giants-infrared observation
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Physics Letters A 182 (1993), S. 353-355 
    ISSN: 0375-9601
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Saethre-Chotzen syndrome is an autosomal dominant acrocephalosyndactyly syndrome whose gene has been assigned to chromosome 7p. Cytogenetic and linkage analyses have enabled the interval encompassing the disease gene to be delimited to a short region of chromosome 7p15.3–p21.2. Based on the genetic analysis of three unreported families, we confirm the location of the disease gene(s) in the interval defined by loci D7S664 and D7S493 (Zmax = 4.78 at * = 0 at the D7S488 locus) but fail to decide whether one or more disease-causing genes map in this genetic interval.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-2323
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Le mauvais pronostic des carcinomes hépatocellulaires (CHC) est en partie dû à l'impossibilité de réséquer chirurgicalement la plupart de ces cancers. Il est à espérer, cependant, qu'avec les progrès des thérapies locorégionales et multidisciplinaires, un certain nombre de ces cancers a priori non résécables, deviennent résécables. Pendant la période 1960–1994, 72 des 663 patients ayant un CHC, vérifiés non résécables chirurgicalement, ont été ainsi traités. On a réussi ainsi à diminuer le diamètre moyen de ces tumeurs de 10 à 5 cm, essentiellement en combinant la ligature en aval de l'artère hépatique, la perfusion directe dans cette artère en amont, une immunoradiothérapie et une radiothérapie régionale fractionnée. L'intervalle entre la première intervention et la résection séquentielle a été de 5 mois. La mortalité opératoire a été de 1.4% pour la résection séquentielle et la survie à 5 ans de 62.1% Les nodules simples, bien encapsulés, situés au lobe droit ou au hile, associés à une cirrhose micronodulaire, et traités avec plusieurs de ces tactiques thérapeutiques, avaient un taux de résecabilité plus élevé par rapport aux autres tumeurs. La survie a été meilleure lorsque la résection a intéressé une tumeur unique dans un seul lobe, sans embolie tumorale, et sans cancer résiduel dans la pièce de résection. On suggère que les CHC localisés, solitaires, bien encapsulés du lobe droit ou du hile, associés à une cirrhose micronodulaire mais chirurgicalement non résécables, sont susceptibles de le devenir avec une technique de cytoréduction. Le pronostic des tumeurs unilatérales, sans embolie tumorale et avec une nécrose tumorale complète est meilleur après traitement multidisciplinaire.
    Abstract: Resumen El mal pronóstico del carcinoma hepatocelular (CHC) se debe, por lo menos en parte, a que en la mayoría de los pacientes el tumor se presenta como una lesión no resecable. Afortunadamente, con el avance en las terapias regionales del cácer y los tratamientos multimodales, algunos de los CHCs no resecables pueden ser convertidos a resecables. En el período 1960–1994, 72 de 663 pacientes con CHCs quirúrgicamente no resecables han sido convertidos a resecables. Se logró una citorreducción exitosa con una disminución promedio del diámetro de 10 cm a 5 cm, fundamentalmente como resultado de un tratamiento combinado doble o triple con ligadura de la arteria hepática, canulación e infusión de la arteria hepática, radioinmunoterapia y radioterapia regional fraccionada. El intervalo entre la primera operación y la resección secuencial fue de cinco meses. La mortalidad operatoria fue 1.4% para la resección secuencial consobrevida a 5 años de 62.1%. El análisis de los factores que influyen sobre la tasa de resección secuencial reveló que un nódulo único, bien encapsufado, ubicados en el lóbulo derecho o en el hilio hepático, asociado con cirrosis micronodular, tratado con modalidades ombinadas dobles o triples, exhibe una tasa de resección secuencial más alta que la observada en el resto de los casos. El análisis de los factores que influyen sobre la sobrevida luego de la resección secuencial reveló que un tumor solitario confinado a un lóbulo, libre de trombos tumorales, sin cáncer residual en el espécimen de la resección secuencial, exhibe la más larga supervivencia. Se sugiere que los CHCs localizados no resecables, solitarios, bien encapsulados, ubicados en el lóbulo derecho o en la región hiliar y asociados con cirrosis micronodular, son buenos candidatos para citorreducción y resección secuencial; y la lesión unilateral, libre de tumor embólico, con necrosis completa del tumor luego de tratamiento multimodal tiende a un mejor pronóstico.
    Notes: Abstract The poor prognosis of hepatocellular carcinoma (HCC) was partly a result of the majority of unresectable HCCs in clinical patients. Fortunately, with the progress of regional cancer therapies and multimodality treatment, some of the localized unresectable HCCs were converted to resectable ones. During the period 1960–1994, 72 of the 663 patients with surgically verified unresectable HCCs have been converted to resectable. Successful cytoreduction with median diameter reduced from 10 cm to 5 cm was mainly a result of the triple or double combination treatment with hepatic artery ligation, hepatic artery cannulation with infusion, radioimmunotherapy, and fractionated regional radiotherapy. The interval between the first operation and the sequential resection was 5 months. The operative mortality was 1.4% for sequential resection, and the 5-year survival was 62.1%. Analysis of factors influencing sequential rescction rate revealed HCCs that were single nodule, well encapsulated, situated at right lobe or hepatic hilum, associated with micronodular cirrhosis, and treated with triple or double combination modalities had higher sequential resection rate as compared to their counterparts. Analysis of factors influencing survival after sequential resection revealed that HCCs with a solitary tumor confined in one lobe, without tumor embolus, and without residual cancer in specimen of sequential resection, had longer survival. It is suggested that localized unresectable, solitary, well encapsulated, right lobe or hilar HCC, associated with micronodular cirrhosis, will be good candidates for cytoreduction and sequential resection; and HCCs with unilateral involvement, without tumor embolus, and with complete necrosis of tumor after multimodality treatment favored better prognosis.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Previous studies showed that levels of some glycosphingolipids (GSLs) expressed in solid brain tumors grown in vivo were reduced or undetectable in cultured cells prepared from the tumors. This phenomenon has been attributed either to suppressed glycolipid synthesis from unknown forces of the tissue culture environment or to the absence of host cells that normally infiltrate the solid tumors growing in vivo. To test further the host cell hypothesis, we examined host cell markers in two experimental mouse brain tumors, the ependymoblastoma and the CT-2A, that were grown as subcutaneous solid tumors in the flank of C57BL/6J (B6) mice or as cultured cells in vitro. The markers included ganglioside N-glycolylneuraminic acid (NeuGc), GA1 (asialo-GM1), and Fc receptor-bearing cells. NeuGc-containing gangliosides, GA1, and Fc receptors are expressed by macrophages and lymphoid-type cells of the mouse host immune system but are not normally expressed by mouse neural cells. Differences in the relative content of Fc receptor-bearing cells in ependymoblastoma and CT-2A tumors grown in vivo (8.3 and 16.8%, respectively) were proportional to differences in the relative content of NeuGc-containing gangliosides (25.5 and 45.1%) and GA1 (8.5 and 13.8%), respectively. Neither cultured tumor cell line expressed Fc receptors, GA1, or NeuGc-containing gangliosides. These findings suggest that non-neoplastic host infiltrating cells (macrophages) contribute significantly to the GSL composition of solid tumors growing in vivo.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract:  The tight skin (Tsk) mouse develops many pathological changes seen in human scleroderma, such as increased collagen content and mast cell density. Although associations between mast cell expansion and skin fibrosis have been reported, the mechanisms underlying mast cell accumulation remain unclear. In this study, we have measured the density of skin mast cells in Tsk mice and their normal littermates (pa/pa) of 4–36 weeks of age, and in the skin heterografted between Tsk and pa/pa mice. Cytokines related to mast cell differentiation, proliferation and migration were examined by using RNase protection assays. Skin mast cell density in Tsk mice was significantly increased from 12 weeks of age, compared to that in pa/pa mice. The expression of transforming growth factor-β1 (TGF-β1), and to a lesser extent, stem cell factor (SCF) and interleukin-15 (IL-15) mRNA was higher in Tsk mice, compared to that in control mice. Mast cell density was unchanged in Tsk skin grafted onto pa/pa hosts, but dramatically increased in pa/pa skin grafted onto Tsk hosts. This latter mast cell hyperplasia was associated with the increases in mRNA levels of TGF-β1, SCF and IL-15, whereas little change in cytokine levels was seen in heterografted Tsk skin. These results suggest that locally produced cytokines in Tsk skin influence mast cell accumulation in this animal model of human scleroderma.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Molecular approaches to understanding the functional circuitry of the nervous system promise new insights into the relationship between genes, brain and behaviour. The cellular diversity of the brain necessitates a cellular resolution approach towards understanding the functional genomics of the ...
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    [s.l.] : Macmillian Magazines Ltd.
    Nature 435 (2005), S. 911-915 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] The atomic structure of tubulin in a polymerized, straight protofilament is clearly distinct from that in a curved conformation bound to a cellular depolymerizer. The nucleotide contents are identical, and in both cases the conformation of the GTP-containing, intra-dimer interface is ...
    Type of Medium: Electronic Resource
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