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  • 1
    Keywords: DISEASE ; BREAST ; COMMON VARIANT ; PULMONARY-FIBROSIS ; GENOME-WIDE ASSOCIATION ; TERT ; CANCER SUSCEPTIBILITY LOCI ; 5P15.33 ; IMMEnSE consortium ; 6P21.33
    Abstract: Compelling biological and epidemiological evidences point to a key role of genetic variants of the TERT and TERC genes in cancer development. We analyzed the genetic variability of these two gene regions using samples of 2,267 multiple myeloma (MM) cases and 2,796 healthy controls. We found that a TERT variant, rs2242652, is associated with reduced MM susceptibility (OR=0.81; 95% CI: 0.72-0.92; p=0.001). In addition we measured the leukocyte telomere length (LTL) in a subgroup of 140 cases who were chemotherapy-free at the time of blood donation and 468 controls, and found that MM patients had longer telomeres compared to controls (OR=1.19; 95% CI: 0.63-2.24; p(trend)=0.01 comparing the quartile with the longest LTL versus the shortest LTL). Our data suggest the hypothesis of decreased disease risk by genetic variants that reduce the efficiency of the telomerase complex. This reduced efficiency leads to shorter telomere ends, which in turn may also be a marker of decreased MM risk. What's new? A critical element of cancer cell immortality is the maintenance of telomere length, a process that is influenced in part by genetic variations in telomerase reverse transcriptase (TERT) and telomerase RNA component (TERC). At the TERT locus in particular, certain variations are linked with either increased or decreased risk of a variety of malignancies. In the present study, a variant of TERT known as rs2242652 was associated with reduced risk of multiple myeloma. Compared with controls, patients with multiple myeloma were found to possess longer telomeres, suggesting an association between increased telomere length and increased multiple myeloma risk.
    Type of Publication: Journal article published
    PubMed ID: 25066524
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  • 2
    Keywords: EXPRESSION ; VISUALIZATION ; RISK ; CANCER PATIENTS ; centrosome ; MOLECULAR CLASSIFICATION ; MONOCLONAL GAMMOPATHY ; UNDETERMINED SIGNIFICANCE ; BLOOD STEM-CELLS ; DATA SETS
    Abstract: Here we perform the first genome-wide association study (GWAS) of multiple myeloma (MM) survival. In a meta-analysis of 306 MM patients treated at UCSF and 239 patients treated at the Mayo clinic, we find a significant association between SNPs near the gene FOPNL on chromosome 16p13 and survival (rs72773978; P=6 x 10(-10)). Patients with the minor allele are at increased risk for mortality (HR: 2.65; 95% CI: 1.94-3.58) relative to patients homozygous for the major allele. We replicate the association in the IMMEnSE cohort including 772 patients, and a University of Utah cohort including 318 patients (rs72773978 P=0.044). Using publicly available data, we find that the minor allele was associated with increased expression of FOPNL and increased expression of FOPNL was associated with higher expression of centrosomal genes and with shorter survival. Polymorphisms at the FOPNL locus are associated with survival among MM patients.
    Type of Publication: Journal article published
    PubMed ID: 26198393
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  • 3
    Abstract: Multiple myeloma (MM) is a malignancy of plasma cells usually infiltrating the bone marrow, associated with the production of a monoclonal immunoglobulin (M protein) which can be detected in the blood and/or urine. Multiple lines of evidence suggest that genetic factors are involved in MM pathogenesis, and several studies have identified single nucleotide polymorphisms (SNPs) associated with the susceptibility to the disease. SNPs within miRNA-binding sites in target genes (miRSNPs) may alter the strength of miRNA-mRNA interactions, thus deregulating protein expression. MiRSNPs are known to be associated with risk of various types of cancer, but they have never been investigated in MM. We performed an in silico genome-wide search for miRSNPs predicted to alter binding of miRNAs to their target sequences. We selected 12 miRSNPs and tested their association with MM risk. Our study population consisted of 1,832 controls and 2,894 MM cases recruited from 7 European countries and Israel in the context of the IMMEnSE (International Multiple Myeloma rESEarch) consortium. In this population two SNPs showed an association with p〈0.05: rs286595 (located in gene MRLP22) and rs14191881 (located in gene TCF19). Results from IMMEnSE were meta-analyzed with data from a previously published genome-wide association study (GWAS). The SNPs rs13409 (located in the 3'UTR of the POU5F1 gene), rs1419881 (TCF19), rs1049633, rs1049623 (both in DDR1) showed significant associations with MM risk. In conclusion, we sought to identify genetic polymorphisms associated with MM risk starting from genome-wide prediction of miRSNPs. For some mirSNPs we have shown promising associations with MM risk. This article is protected by copyright. All rights reserved.
    Type of Publication: Journal article published
    PubMed ID: 27718532
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  • 4
    ISSN: 1434-6036
    Keywords: PACS. 75.10.Dg Crystal-field theory and spin Hamiltonians - 75.10.Jm Quantized spin models - 75.30.Gw Magnetic anisotropy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract: The zero temperature phase diagram of a one-dimensional ferromagnet with cubic single ion anisotropy in an external magnetic field is studied. The mean-field approximation and the density-matrix renormalization group method are applied. Two phases at finite magnetic fields are identified: a canted phase with spontaneously broken symmetry and a phase with magnetization along the magnetic field. Both methods predict that the canted phase exists even for the single-ion anisotropy strong enough to destroy the magnetic order at zero magnetic field. In contrast to the mean-field theory, the density-matrix renormalization group predicts a reentrant behavior for the model. The character of the phase transition at finite magnetic field has also been considered and the critical index has been found.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1434-6036
    Keywords: PACS. 75.10.Dg Crystal-field theory and spin Hamiltonians - 75.10.Jm Quantized spin models - 75.30.Gw Magnetic anisotropy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract: The ground state properties of S =2 ferromagnets with isotropic Heisenberg exchange (J) and single-ion cubic anisotropy (D) are studied. The perturbation theory for is used to find an effective Hamiltonian up to the fourth order for 1, 2 and 3 dimensions. It is shown that in opposition to the MFA prediction there is the quadrupolar long range order at T = 0 in the non-magnetic state of the system without a quadrupolar type of interaction. The effect is a consequence of the quantum nature of the model.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1573-1561
    Keywords: rabbit ; Oryctolagus cuniculus ; odors ; anal ; inguinal ; chin glands ; urine ; territorial confidence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract In 14 series, each of 100 tests, involving 350 individual animals it has been shown that odors derived from the anal, inguinal and chin glands and urine strengthen to different degrees the confidence of European wild rabbits,Oryctolagus cuniculus. In the tests, two rabbits were put together on otherwise neutral ground previously treated with the odor from one of the contestants. The confidence of the rabbits was determined from an assessment of the record of the time to first physical contact, the frequencies of approaches and aggression, the number of attempts to escape, and also by making a subjective assessment of their general deportment. The results confirm earlier conclusions on the territorial functions of the anal and chin glands, the role of inguinal glands in individual identification, and the behavioral role of urine. On otherwise neutral ground the rabbits' own chin secretions were found to be the most effective in stimulating the confidence of males and that of their female partners. The odor of the anal gland secretions of males stimulated a similar but slightly weaker effect. The anal gland secretions of females influenced their own confidence but not that of males. Urine seemed to play a more important role in affecting the confidence of females than of males. Inguinal gland secretions had least effect. Odor from this source generally did not influence the confidence of the experimental animals; secretion from the inguinal glands of males had a slight effect on the behavior of their female partners.
    Type of Medium: Electronic Resource
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