1. |
- Couch, Fergus J., et al.
(author)
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Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer
- 2016
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In: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 7:11375, s. 1-13
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Journal article (peer-reviewed)abstract
- Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 x 10(-8)) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for similar to 11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction.
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2. |
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3. |
- Adamczewski-Musch, J., et al.
(author)
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Production and electromagnetic decay of hyperons : a feasibility study with HADES as a phase-0 experiment at FAIR
- 2021
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In: European Physical Journal A. - : Springer Nature. - 1434-6001 .- 1434-601X. ; 57:4
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Journal article (peer-reviewed)abstract
- A feasibility study has been performed in order to investigate the performance of the HADES detector to measure the electromagnetic decays of the hyperon resonances Sigma(1385)(0), Lambda(1405) and Lambda(1520) as well as the production of double strange baryon systems Xi(-) and Lambda Lambda in p + p reactions at a beam kinetic energy of 4.5GeV. The existing HADES detector will be upgraded by a new Forward Detector, which extends the detector acceptance into a range of polar angles that plays a crucial role for these investigations. The analysis of each channel is preceded by a consideration of the production cross-sections. Afterwards the expected signal count rates using a target consisting of either liquid hydrogen or polyethylene are summarized.
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4. |
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5. |
- Barrdahl, Myrto, et al.
(author)
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Post-G WAS gene-environment interplay in breast cancer : results from the Breast and Prostate Cancer Cohort Consortium and a meta-analysis on 79 000 women
- 2014
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In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:19, s. 5260-5270
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Journal article (peer-reviewed)abstract
- We studied the interplay between 39 breast cancer (BC) risk SNPs and established BC risk (body mass index, height, age at menarche, parity, age at menopause, smoking, alcohol and family history of BC) and prognostic factors (TNM stage, tumor grade, tumor size, age at diagnosis, estrogen receptor status and progesterone receptor status) as joint determinants of BC risk. We used a nested case-control design within the National Cancer Institute's Breast and Prostate Cancer Cohort Consortium (BPC3), with 16 285 BC cases and 19 376 controls. We performed stratified analyses for both the risk and prognostic factors, testing for heterogeneity for the risk factors, and case-case comparisons for differential associations of polymorphisms by subgroups of the prognostic factors. We analyzed multiplicative interactions between the SNPs and the risk factors. Finally, we also performed a meta-analysis of the interaction ORs from BPC3 and the Breast Cancer Association Consortium. After correction for multiple testing, no significant interaction between the SNPs and the established risk factors in the BPC3 study was found. The meta-analysis showed a suggestive interaction between smoking status and SLC4A7-rs4973768 (P-interaction = 8.84 x 10(-4)) which, although not significant after considering multiple comparison, has a plausible biological explanation. In conclusion, in this study of up to almost 79 000 women we can conclusively exclude any novel major interactions between genome-wide association studies hits and the epidemiologic risk factors taken into consideration, but we propose a suggestive interaction between smoking status and SLC4A7-rs4973768 that if further replicated could help our understanding in the etiology of BC.
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6. |
- Barucca, G., et al.
(author)
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Feasibility studies for the measurement of time-like proton electromagnetic form factors from (p)over-barp -> mu(+)mu(-) at PANDA at FAIR
- 2021
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In: European Physical Journal A. - NEW YORK, USA : Springer Nature. - 1434-6001 .- 1434-601X. ; 57:1
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Journal article (peer-reviewed)abstract
- This paper reports on Monte Carlo simulation results for future measurements of the moduli of time-like proton electromagnetic form factors, vertical bar G(E)vertical bar and vertical bar G(M)vertical bar, using the (p) over barp -> mu(+)mu(-) reaction at PANDA (FAIR). The electromagnetic form factors are fundamental quantities parameterizing the electric and magnetic structure of hadrons. This work estimates the statistical and total accuracy with which the form factors can be measured at PANDA, using an analysis of simulated data within the PandaRoot software framework. The most crucial background channel is (p) over barp -> pi(+)pi(-), due to the very similar behavior of muons and pions in the detector. The suppression factors are evaluated for this and all other relevant background channels at different values of antiproton beam momentum. The signal/background separation is based on a multivariate analysis, using the Boosted Decision Trees method. An expected background subtraction is included in this study, based on realistic angular distributions of the background contribution. Systematic uncertainties are considered and the relative total uncertainties of the form factor measurements are presented.
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7. |
- Barucca, G., et al.
(author)
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PANDA Phase One
- 2021
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In: European Physical Journal A. - : Springer Nature. - 1434-6001 .- 1434-601X. ; 57:6
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Journal article (peer-reviewed)abstract
- The Facility for Antiproton and Ion Research (FAIR) in Darmstadt, Germany, provides unique possibilities for a new generation of hadron-, nuclear- and atomic physics experiments. The future antiProton ANnihilations at DArmstadt (PANDA or PANDA) experiment at FAIR will offer a broad physics programme, covering different aspects of the strong interaction. Understanding the latter in the non-perturbative regime remains one of the greatest challenges in contemporary physics. The antiproton-nucleon interaction studied with PANDA provides crucial tests in this area. Furthermore, the high-intensity, low-energy domain of PANDA allows for searches for physics beyond the Standard Model, e.g. through high precision symmetry tests. This paper takes into account a staged approach for the detector setup and for the delivered luminosity from the accelerator. The available detector setup at the time of the delivery of the first antiproton beams in the HESR storage ring is referred to as the Phase One setup. The physics programme that is achievable during Phase One is outlined in this paper.
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8. |
- Barucca, G., et al.
(author)
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Precision resonance energy scans with the PANDA experiment at FAIR : Sensitivity study for width and line shape measurements of the X(3872)
- 2019
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In: European Physical Journal A. - : SPRINGER. - 1434-6001 .- 1434-601X. ; 55:3
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Journal article (peer-reviewed)abstract
- This paper summarises a comprehensive Monte Carlo simulation study for precision resonance energy scan measurements. Apart from the proof of principle for natural width and line shape measurements of very narrow resonances with PANDA, the achievable sensitivities are quantified for the concrete example of the charmonium-like X(3872) state discussed to be exotic, and for a larger parameter space of various assumed signal cross-sections, input widths and luminosity combinations. PANDA is the only experiment that will be able to perform precision resonance energy scans of such narrow states with quantum numbers of spin and parities that differ from JPC=1--.
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9. |
- Barucca, G., et al.
(author)
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Study of excited Ξ baryons with the P¯ ANDA detector
- 2021
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In: European Physical Journal A. - : Springer Nature. - 1434-6001 .- 1434-601X. ; 57:4
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Journal article (peer-reviewed)abstract
- The study of baryon excitation spectra provides insight into the inner structure of baryons. So far, most of the world-wide efforts have been directed towards N∗ and Δ spectroscopy. Nevertheless, the study of the double and triple strange baryon spectrum provides independent information to the N∗ and Δ spectra. The future antiproton experiment P¯ANDA will provide direct access to final states containing a Ξ¯ Ξ pair, for which production cross sections up to μb are expected in p¯p reactions. With a luminosity of L= 10 31 cm- 2 s- 1 in the first phase of the experiment, the expected cross sections correspond to a production rate of ∼106events/day. With a nearly 4 π detector acceptance, P¯ANDA will thus be a hyperon factory. In this study, reactions of the type p¯p → Ξ¯ +Ξ∗ - as well as p¯p → Ξ¯ ∗ +Ξ- with various decay modes are investigated. For the exclusive reconstruction of the signal events a full decay tree fit is used, resulting in reconstruction efficiencies between 3 and 5%. This allows high statistics data to be collected within a few weeks of data taking.
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10. |
- Barucca, G., et al.
(author)
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The potential of Λ and Ξ- studies with PANDA at FAIR
- 2021
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In: European Physical Journal A. - : Springer Nature. - 1434-6001 .- 1434-601X. ; 57:4
-
Journal article (peer-reviewed)abstract
- The antiproton experiment PANDA at FAIR is designed to bring hadron physics to a new level in terms of scope, precision and accuracy. In this work, its unique capability for studies of hyperons is outlined. We discuss ground-state hyperons as diagnostic tools to study non-perturbative aspects of the strong interaction, and fundamental symmetries. New simulation studies have been carried out for two benchmark hyperon-antihyperon production channels: p¯ p→ Λ¯ Λ and p¯ p→ Ξ¯ +Ξ-. The results, presented in detail in this paper, show that hyperon-antihyperon pairs from these reactions can be exclusively reconstructed with high efficiency and very low background contamination. In addition, the polarisation and spin correlations have been studied, exploiting the weak, self-analysing decay of hyperons and antihyperons. Two independent approaches to the finite efficiency have been applied and evaluated: one standard multidimensional efficiency correction approach, and one efficiency independent approach. The applicability of the latter was thoroughly evaluated for all channels, beam momenta and observables. The standard method yields good results in all cases, and shows that spin observables can be studied with high precision and accuracy already in the first phase of data taking with PANDA.
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11. |
- Campa, Daniele, et al.
(author)
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A genome-wide "pleiotropy scan'' does not identify new susceptibility loci for estrogen receptor negative breast cancer
- 2014
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:2, s. e85955-
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Journal article (peer-reviewed)abstract
- Approximately 15-30% of all breast cancer tumors are estrogen receptor negative (ER-). Compared with ER- positive (ER+) disease they have an earlier age at onset and worse prognosis. Despite the vast number of risk variants identified for numerous cancer types, only seven loci have been unambiguously identified for ER- negative breast cancer. With the aim of identifying new susceptibility SNPs for this disease we performed a pleiotropic genome-wide association study (GWAS). We selected 3079 SNPs associated with a human complex trait or disease at genome-wide significance level (P<5x10(-8)) to perform a secondary analysis of an ER- negative GWAS from the National Cancer Institute's Breast and Prostate Cancer Cohort Consortium (BPC3), including 1998 cases and 2305 controls from prospective studies. We then tested the top ten associations (i.e. with the lowest P-values) using three additional populations with a total sample size of 3509 ER+ cases, 2543 ER- cases and 7031 healthy controls. None of the 3079 selected variants in the BPC3 ER- GWAS were significant at the adjusted threshold. 186 variants were associated with ER- breast cancer risk at a conventional threshold of P<0.05, with P-values ranging from 0.049 to 2.3 x 10(-4). None of the variants reached statistical significance in the replication phase. In conclusion, this study did not identify any novel susceptibility loci for ER-breast cancer using a "pleiotropic approach''.
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12. |
- Dainese, Matteo, et al.
(author)
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Landscape simplification weakens the association between terrestrial producer and consumer diversity in Europe
- 2017
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In: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 23:8, s. 3040-3051
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Journal article (peer-reviewed)abstract
- Land-use change is one of the primary drivers of species loss, yet little is known about its effect on other components of biodiversity that may be at risk. Here, we ask whether, and to what extent, landscape simplification, measured as the percentage of arable land in the landscape, disrupts the functional and phylogenetic association between primary producers and consumers. Across seven European regions, we inferred the potential associations (functional and phylogenetic) between host plants and butterflies in 561 seminatural grasslands. Local plant diversity showed a strong bottom-up effect on butterfly diversity in the most complex landscapes, but this effect disappeared in simple landscapes. The functional associations between plant and butterflies are, therefore, the results of processes that act not only locally but are also dependent on the surrounding landscape context. Similarly, landscape simplification reduced the phylogenetic congruence among host plants and butterflies indicating that closely related butterflies become more generalist in the resources used. These processes occurred without any detectable change in species richness of plants or butterflies along the gradient of arable land. The structural properties of ecosystems are experiencing substantial erosion, with potentially pervasive effects on ecosystem functions and future evolutionary trajectories. Loss of interacting species might trigger cascading extinction events and reduce the stability of trophic interactions, as well as influence the longer term resilience of ecosystem functions. This underscores a growing realization that species richness is a crude and insensitive metric and that both functional and phylogenetic associations, measured across multiple trophic levels, are likely to provide additional and deeper insights into the resilience of ecosystems and the functions they provide.
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13. |
- Davi, F., et al.
(author)
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Technical design report for the endcap disc DIRC
- 2022
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In: Journal of Physics G. - : Institute of Physics Publishing (IOPP). - 0954-3899 .- 1361-6471. ; 49:12
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Journal article (peer-reviewed)abstract
- PANDA (anti-proton annihiliation at Darmstadt) is planned to be one of the four main experiments at the future international accelerator complex FAIR (Facility for Antiproton and Ion Research) in Darmstadt, Germany. It is going to address fundamental questions of hadron physics and quantum chromodynamics using cooled antiproton beams with a high intensity and and momenta between 1.5 and 15 GeV/c. PANDA is designed to reach a maximum luminosity of 2 × 1032 cm−2 s. Most of the physics programs require an excellent particle identification (PID). The PID of hadronic states at the forward endcap of the target spectrometer will be done by a fast and compact Cherenkov detector that uses the detection of internally reflected Cherenkov light (DIRC) principle. It is designed to cover the polar angle range from 5° to 22° and to provide a separation power for the separation of charged pions and kaons up to 3 standard deviations (s.d.) for particle momenta up to 4 GeV/c in order to cover the important particle phase space. This document describes the technical design and the expected performance of the novel PANDA disc DIRC detector that has not been used in any other high energy physics experiment before. The performance has been studied with Monte-Carlo simulations and various beam tests at DESY and CERN. The final design meets all PANDA requirements and guarantees sufficient safety margins.
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14. |
- Dongre, Mitesh, et al.
(author)
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Flagella-mediated secretion of a novel Vibrio cholerae cytotoxin affecting both vertebrate and invertebrate hosts
- 2018
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In: Communications Biology. - : Springer Nature Publishing AG. - 2399-3642. ; 1
-
Journal article (peer-reviewed)abstract
- Using Caenorhabditis elegans as an infection host model for Vibrio cholerae predator interactions, we discovered a bacterial cytotoxin, MakA, whose function as a virulence factor relies on secretion via the flagellum channel in a proton motive force-dependent manner. The MakA protein is expressed from the polycistronic makDCBA (motility-associated killing factor) operon. Bacteria expressing makDCBA induced dramatic changes in intestinal morphology leading to a defecation defect, starvation and death in C. elegans. The Mak proteins also promoted V. cholerae colonization of the zebrafish gut causing lethal infection. A structural model of purified MakA at 1.9 Å resolution indicated similarities to members of a superfamily of bacterial toxins with unknown biological roles. Our findings reveal an unrecognized role for V. cholerae flagella in cytotoxin export that may contribute both to environmental spread of the bacteria by promoting survival and proliferation in encounters with predators, and to pathophysiological effects during infections.
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15. |
- Flodbring Larsson, Per, et al.
(author)
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FcγRIIIa receptor interacts with androgen receptor and PIP5K1α to promote growth and metastasis of prostate cancer
- 2022
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In: Molecular Oncology. - : John Wiley & Sons. - 1574-7891 .- 1878-0261.
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Journal article (peer-reviewed)abstract
- Low-affinity immunoglobulin gamma Fc region receptor III-A (FcγRIIIa) is a cell surface protein that belongs to a family of Fc receptors that facilitate the protective function of the immune system against pathogens. However, the role of FcγRIIIa in prostate cancer (PCa) progression remained unknown. In this study, we found that FcγRIIIa expression was present in PCa cells and its level was significantly higher in metastatic lesions than in primary tumors from the PCa cohort (P = 0.006). PCa patients with an elevated level of FcγRIIIa expression had poorer biochemical recurrence (BCR)-free survival compared with those with lower FcγRIIIa expression, suggesting that FcγRIIIa is of clinical importance in PCa. We demonstrated that overexpression of FcγRIIIa increased the proliferative ability of PCa cell line C4-2 cells, which was accompanied by the upregulation of androgen receptor (AR) and phosphatidylinositol-4-phosphate 5-kinase alpha (PIP5Kα), which are the key players in controlling PCa progression. Conversely, targeted inhibition of FcγRIIIa via siRNA-mediated knockdown or using its inhibitory antibody suppressed growth of xenograft PC-3 and PC-3M prostate tumors and reduced distant metastasis in xenograft mouse models. We further showed that elevated expression of AR enhanced FcγRIIIa expression, whereas inhibition of AR activity using enzalutamide led to a significant downregulation of FcγRIIIa protein expression. Similarly, inhibition of PIP5K1α decreased FcγRIIIa expression in PCa cells. FcγRIIIa physically interacted with PIP5K1α and AR via formation of protein-protein complexes, suggesting that FcγRIIIa is functionally associated with AR and PIP5K1α in PCa cells. Our study identified FcγRIIIa as an important factor in promoting PCa growth and invasion. Further, the elevated activation of FcγRIII and AR and PIP5K1α pathways may cooperatively promote PCa growth and invasion. Thus, FcγRIIIa may serve as a potential new target for improved treatment of metastatic and castration-resistant PCa.
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16. |
- Franzén-Dahlin, Åsa, et al.
(author)
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A randomized controlled trial evaluating the effect of a support and education programme for spouses of people affected by stroke
- 2008
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In: Clinical Rehabilitation. - : SAGE Publications. - 0269-2155 .- 1477-0873. ; 22:8, s. 722-30
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To determine whether a nurse-led support and education programme for spouses of patients affected by stroke improved the psychological health of the spouses.DESIGN: A longitudinal, open, randomized controlled trial.SAMPLE: One hundred spouses of stroke patients were randomly assigned to either an intervention or a control group.SETTING: The study was conducted in a hospital setting.INTERVENTION: The intervention consisted of six group meetings during six months, with a follow-up after further six months. Comparison between the intervention and the control groups was made at baseline, after six and 12 months using analysis with repeated measures.MAIN MEASURES: The Comprehensive Psychopathological Rating Scale--Self-Affective for psychological health.RESULTS: No significant difference was found between the intervention and control groups concerning overall psychological health. However, a subanalysis revealed that those who participated more frequently in the group meetings (five or six times) had significantly stronger psychological health (P<0.05). Knowledge about stroke increased over time in both groups, but participants in the intervention group learned more (P=0.041).CONCLUSION: Encouraging participation in the group meetings of a support programme might have a positive effect on psychological health.
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17. |
- Franzén-Dahlin, Åsa, et al.
(author)
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Predictors of life situation among significant others of depressed or aphasic stroke patients
- 2008
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In: Journal of Clinical Nursing. - : Wiley. - 0962-1067 .- 1365-2702. ; 17:12, s. 1574-1580
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Journal article (peer-reviewed)abstract
- AIM: The aim of this study was to examine predictors of the life situation of the significant other of depressed or aphasic stroke patients.BACKGROUND: Depression and aphasia are common consequences of stroke, and both may put pressure on the significant other who have to deal not only with a possible physical handicap but also with communication and/or serious psychiatric difficulties.DESIGN: Descriptive, cross-sectional study.METHODS: The participants were significant others of 71 depressed and 77 aphasic stroke patients. Depression was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorder, and degree of aphasia was diagnosed with the Amsterdam Nijmegen Everyday Language Test. Assessments of the life situation, state of depression and aggression, personality change and need of assistance were made through questionnaires issued to the significant others.RESULTS: Perceived need of assistance was the only common predictor of life situation of the significant other in both groups (p < 0.001). With respect to the aphasic patients, perceived personality change (p < 0.001) and living with the patient (p = 0.004) were factors that had a negative effect on the life situation of the significant other.CONCLUSIONS: This study highlights that the perception of the patient's need of assistance is an important factor in predicting the life situation among spouses of depressed as well as aphasic stroke patients. A comparison of the two groups to explain the life situation of the significant others revealed greater explanatory power for the aphasic group.RELEVANCE TO CLINICAL PRACTICE: Assessments of the spouses' perception as well as of the patients' factual situation may identify those significant others at risk. With this new approach, necessary steps may be taken to alleviate pressure on the significant other.
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18. |
- Franzén-Dahlin, Åsa, et al.
(author)
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Predictors of psychological health in spouses of persons affected by stroke
- 2007
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In: Journal of Clinical Nursing. - : Wiley. - 0962-1067 .- 1365-2702. ; 16:5, s. 885-891
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Journal article (peer-reviewed)abstract
- AIM: To identify predictors of psychological health and examine if these predictors change over time in spouses of stroke patients during the first year after stroke. A second aim was to identify gender differences in psychological health among the spouses.BACKGROUND: The impact of burden in long-term caregivers may result in psychological consequences for the spouse. The rehabilitation process for the patient can be negatively affected by a stressed caregiver and result in long-term hospitalization. To identify spouses at risk for physical and psychological distress is, therefore, essential to support those in need.DESIGN: Longitudinal, comparative study.METHODS: One hundred spouses of stroke patients were assessed at baseline, as well as after six and 12 months, regarding psychological health, well-being, own illness, need of assistance from general practitioner and/or district nurse, social network and knowledge about stroke. Stepwise multiple regression analyses were conducted for baseline, six- and 12-month assessments, respectively, with psychological health as the dependent variable.RESULTS: General well-being and presence of illness in spouse were the most prominent predictors of psychological health, throughout the first year.CONCLUSIONS: Enhancing psychological health and preventing medical problems in the caregiver are essential considerations to enable patients with stroke-related disabilities to continue to live at home.RELEVANCE TO CLINICAL PRACTICE: Evaluating the situation for spouses of stroke patients is an important component when planning for the future care of the patient.
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19. |
- Gomzikova, Marina O., et al.
(author)
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Cytochalasin B-induced membrane vesicles convey angiogenic activity of parental cells
- 2017
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In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 8:41, s. 70496-70507
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Journal article (peer-reviewed)abstract
- Naturally occurring extracellular vesicles (EVs) play essential roles in intracellular communication and delivery of bioactive molecules. Therefore it has been suggested that EVs could be used for delivery of therapeutics. However, to date the therapeutic application of EVs has been limited by number of factors, including limited yield and full understanding of their biological activities. To address these issues, we analyzed the morphology, molecular composition, fusion capacity and biological activity of Cytochalasin B-induced membrane vesicles (CIMVs). The size of these vesicles was comparable to that of naturally occurring EVs. In addition, we have shown that CIMVs from human SH-SY5Y cells contain elevated levels of VEGF as compared to the parental cells, and stimulate angiogenesis in vitro and in vivo.
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20. |
- Granlund, Mats, 1954-, et al.
(author)
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AAC interventions for children in a family environment : Implementing evidence in practice
- 2008
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In: Augmentative and Alternative Communication. - : Informa UK Limited. - 0743-4618 .- 1477-3848. ; 24:3, s. 207-219
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Journal article (peer-reviewed)abstract
- Interventions that focus on implementing augmentative and alternative communication (AAC) strategies and methods have been available to children in need of AAC and their families for at least 30 years. To date, most of the research that has considered AAC in family settings has been focused on gathering evidence of the effects of AAC interventions, rather than on implementing evidence-based strategies in everyday practice to improve outcomes. The purpose of this article is to discuss the research that has focused on parents as AAC interventionists, the family as a context for AAC intervention, and the effects of AAC interventions on children and other family members. The discussion is framed within the four steps associated with the process of knowledge translation: (a) deciding on desired outcomes of interventions, (b) evaluating evidence of the effectiveness of different AAC methods to obtain the desired outcomes, (c) translating the research evidence into everyday practice, and (d) implementing knowledge in practice.
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21. |
- Haiman, Christopher A., et al.
(author)
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A common variant at the TERT-CLPTM1L locus is associated with estrogen receptor-negative breast cancer
- 2011
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:12, s. 61-1210
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Journal article (peer-reviewed)abstract
- Estrogen receptor (ER)-negative breast cancer shows a higher incidence in women of African ancestry compared to women of European ancestry. In search of common risk alleles for ER-negative breast cancer, we combined genome-wide association study (GWAS) data from women of African ancestry (1,004 ER-negative cases and 2,745 controls) and European ancestry (1,718 ER-negative cases and 3,670 controls), with replication testing conducted in an additional 2,292 ER-negative cases and 16,901 controls of European ancestry. We identified a common risk variant for ER-negative breast cancer at the TERT-CLPTM1L locus on chromosome 5p15 (rs10069690: per-allele odds ratio (OR) = 1.18 per allele, P = 1.0 x 10(-10)). The variant was also significantly associated with triple-negative (ER-negative, progesterone receptor (PR)-negative and human epidermal growth factor-2 (HER2)-negative) breast cancer (OR = 1.25, P = 1.1 x 10(-9)), particularly in younger women (<50 years of age) (OR = 1.48, P = 1.9 x 10(-9)). Our results identify a genetic locus associated with estrogen receptor negative breast cancer subtypes in multiple populations.
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22. |
- Hedblom, Andreas, et al.
(author)
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CDK1 interacts with RARγ and plays an important role in treatment response of acute myeloid leukemia
- 2013
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In: Cell Cycle. - : Taylor & Francis. - 1538-4101 .- 1551-4005. ; 12:8, s. 1251-1266
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Journal article (peer-reviewed)abstract
- Alterations in cell cycle pathways and retinoic acid signaling are implicated in leukemogenesis. However, little is known about the roles of cyclin-dependent kinases (CDKs) in treatment response of leukemia. In this study, we observed that CDK1 expression was significantly higher in bone marrow from 42 patients with acute myeloid leukemia (AML) at recurrence than that at first diagnosis (p = 0.04). AML patients had higher level of nuclear CDK1 in their leukemic blasts tended to have poorer clinical outcome compared with those with lower levels. We showed that CDK1 function is required for all-trans retinoic acid (ATRA) to achieve the optimal effect in U-937 human leukemic cells. CDK1 modulates the levels of P27(kip) and AKT phosphorylation in response to ATRA treatment. Further, we show, for the first time, that RARγ in concert with ATRA regulates protein levels of CDK1 and its subcellular localization. The regulation of the subcellular content of CDK1 and RARγ by ATRA is an important process for achieving an effective response in treatment of leukemia. RARγ and CDK1 form a reciprocal regulatory circuit in the nucleus and influence the function and protein stability of each other and the level of P27(kip) protein. In addition, expression of wee1 kinase and Cdc25A/C phosphatases also coincide with CDK1 expression and its subcellular localization in response to ATRA treatment. Our study reveals a novel mechanism by which CDK1 and RARγ coordinate with ATRA to influence cell cycle progression and cellular differentiation.
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23. |
- Jäghult, Susanna, et al.
(author)
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A multiprofessional education programme for patients with inflammatory bowel disease : a randomized controlled trial
- 2007
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In: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 42:12, s. 1452-1459
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Health-related quality of life is impaired in patients with inflammatory bowel disease and improved disease-related information can improve this situation. The aims of this study were to create an education programme that could be readily applicable at the clinic and would be suitable for newly diagnosed patients with inflammatory bowel disease, and to investigate whether the programme could improve their health-related quality of life.MATERIAL AND METHODS: Ninety-three patients with inflammatory bowel disease in remission were included and randomized to an intervention group or a control group. The intervention group attended a multiprofessional education programme while the control group received regular information. Four questionnaires were used for measuring health-related quality of life. Both groups completed the questionnaires at baseline and after 6 months. The intervention group also completed the questionnaires after 1 month.RESULTS: No significant differences were found when comparing the two groups at 6 months. However, the multi-professional education programme was highly appreciated by the patients.CONCLUSIONS: In the present study no improvement could be seen in health-related quality of life in patients with inflammatory bowel disease after participating in an education programme in comparison with the control group. This might be due to the fact that the questionnaires were not sensitive enough or that some patients were not in clinical remission. The patients' enthusiasm for the multiprofessional education programme has led to its being part of the regular care at the clinic.
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24. |
- Karlsson, Richard, et al.
(author)
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Establishment of Prostate Tumor Growth and Metastasis Is Supported by Bone Marrow Cells and Is Mediated by PIP5K1α Lipid Kinase
- 2020
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In: Cancers. - : MDPI. - 2072-6694. ; 12:9
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Journal article (peer-reviewed)abstract
- Cancer cells facilitate growth and metastasis by using multiple signals from the cancer-associated microenvironment. However, it remains poorly understood whether prostate cancer (PCa) cells may recruit and utilize bone marrow cells for their growth and survival. Furthermore, the regulatory mechanisms underlying interactions between PCa cells and bone marrow cells are obscure. In this study, we isolated bone marrow cells that mainly constituted populations that were positive for CD11b and Gr1 antigens from xenograft PC-3 tumor tissues from athymic nu/nu mice. We found that the tumor-infiltrated cells alone were unable to form tumor spheroids, even with increased amounts and time. By contrast, the tumor-infiltrated cells together with PCa cells formed large numbers of tumor spheroids compared with PCa cells alone. We further utilized xenograft athymic nu/nu mice bearing bone metastatic lesions. We demonstrated that PCa cells were unable to survive and give rise to colony-forming units (CFUs) in media that were used for hematopoietic cell colony-formation unit (CFU) assays. By contrast, PC-3M cells survived when bone marrow cells were present and gave rise to CFUs. Our results showed that PCa cells required bone marrow cells to support their growth and survival and establish bone metastasis in the host environment. We showed that PCa cells that were treated with either siRNA for PIP5K1α or its specific inhibitor, ISA-2011B, were unable to survive and produce tumor spheroids, together with bone marrow cells. Given that the elevated expression of PIP5K1α was specific for PCa cells and was associated with the induced expression of VEGF receptor 2 in PCa cells, our findings suggest that cancer cells may utilize PIP5K1α-mediated receptor signaling to recruit growth factors and ligands from the bone marrow-derived cells. Taken together, our study suggests a new mechanism that enables PCa cells to gain proliferative and invasive advantages within their associated host microenvironment. Therapeutic interventions using PIP5K1α inhibitors may not only inhibit tumor invasion and metastasis but also enhance the host immune system.
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25. |
- Kattge, Jens, et al.
(author)
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TRY plant trait database - enhanced coverage and open access
- 2020
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In: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
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Journal article (peer-reviewed)abstract
- Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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