| 1. |
- Aad, G, et al.
(författare)
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- 2015
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swepub:Mat__t
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| 2. |
- Fitzmauric, C., et al.
(författare)
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Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived with Disability, and Disability-Adjusted Life-Years for 29 Cancer Groups, 1990 to 2017 : A Systematic Analysis for the Global Burden of Disease Study
- 2019
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Ingår i: JAMA Oncology. - : American Medical Association. - 2374-2437 .- 2374-2445. ; 5:12, s. 1749-1768
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Cancer and other noncommunicable diseases (NCDs) are now widely recognized as a threat to global development. The latest United Nations high-level meeting on NCDs reaffirmed this observation and also highlighted the slow progress in meeting the 2011 Political Declaration on the Prevention and Control of Noncommunicable Diseases and the third Sustainable Development Goal. Lack of situational analyses, priority setting, and budgeting have been identified as major obstacles in achieving these goals. All of these have in common that they require information on the local cancer epidemiology. The Global Burden of Disease (GBD) study is uniquely poised to provide these crucial data.Objective: To describe cancer burden for 29 cancer groups in 195 countries from 1990 through 2017 to provide data needed for cancer control planning.Evidence Review: We used the GBD study estimation methods to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life-years (DALYs). Results are presented at the national level as well as by Socio-demographic Index (SDI), a composite indicator of income, educational attainment, and total fertility rate. We also analyzed the influence of the epidemiological vs the demographic transition on cancer incidence.Findings: In 2017, there were 24.5 million incident cancer cases worldwide (16.8 million without nonmelanoma skin cancer [NMSC]) and 9.6 million cancer deaths. The majority of cancer DALYs came from years of life lost (97%), and only 3% came from years lived with disability. The odds of developing cancer were the lowest in the low SDI quintile (1 in 7) and the highest in the high SDI quintile (1 in 2) for both sexes. In 2017, the most common incident cancers in men were NMSC (4.3 million incident cases); tracheal, bronchus, and lung (TBL) cancer (1.5 million incident cases); and prostate cancer (1.3 million incident cases). The most common causes of cancer deaths and DALYs for men were TBL cancer (1.3 million deaths and 28.4 million DALYs), liver cancer (572000 deaths and 15.2 million DALYs), and stomach cancer (542000 deaths and 12.2 million DALYs). For women in 2017, the most common incident cancers were NMSC (3.3 million incident cases), breast cancer (1.9 million incident cases), and colorectal cancer (819000 incident cases). The leading causes of cancer deaths and DALYs for women were breast cancer (601000 deaths and 17.4 million DALYs), TBL cancer (596000 deaths and 12.6 million DALYs), and colorectal cancer (414000 deaths and 8.3 million DALYs).Conclusions and Relevance: The national epidemiological profiles of cancer burden in the GBD study show large heterogeneities, which are a reflection of different exposures to risk factors, economic settings, lifestyles, and access to care and screening. The GBD study can be used by policy makers and other stakeholders to develop and improve national and local cancer control in order to achieve the global targets and improve equity in cancer care.
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| 3. |
- Berglund, U. W., et al.
(författare)
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Validation and development of MTH1 inhibitors for treatment of cancer
- 2016
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 27:12, s. 2275-2283
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Tidskriftsartikel (refereegranskat)abstract
- Background: Previously, we showed cancer cells rely on the MTH1 protein to prevent incorporation of otherwise deadly oxidised nucleotides into DNA and we developed MTH1 inhibitors which selectively kill cancer cells. Recently, several new and potent inhibitors of MTH1 were demonstrated to be non-toxic to cancer cells, challenging the utility of MTH1 inhibition as a target for cancer treatment. Material and methods: Human cancer cell lines were exposed in vitro to MTH1 inhibitors or depleted of MTH1 by siRNA or shRNA. 8-oxodG was measured by immunostaining and modified comet assay. Thermal Proteome profiling, proteomics, cellular thermal shift assays, kinase and CEREP panel were used for target engagement, mode of action and selectivity investigations of MTH1 inhibitors. Effect of MTH1 inhibition on tumour growth was explored in BRAF V600E-mutated malignant melanoma patient derived xenograft and human colon cancer SW480 and HCT116 xenograft models. Results: Here, we demonstrate that recently described MTH1 inhibitors, which fail to kill cancer cells, also fail to introduce the toxic oxidized nucleotides into DNA. We also describe a new MTH1 inhibitor TH1579, (Karonudib), an analogue of TH588, which is a potent, selective MTH1 inhibitor with good oral availability and demonstrates excellent pharmacokinetic and anti-cancer properties in vivo. Conclusion: We demonstrate that in order to kill cancer cells MTH1 inhibitors must also introduce oxidized nucleotides into DNA. Furthermore, we describe TH1579 as a best-in-class MTH1 inhibitor, which we expect to be useful in order to further validate the MTH1 inhibitor concept.
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| 4. |
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| 6. |
- Wang, ZC, et al.
(författare)
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Extraction and analysis of signatures from the Gene Expression Omnibus by the crowd
- 2016
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7, s. 12846-
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Tidskriftsartikel (refereegranskat)abstract
- Gene expression data are accumulating exponentially in public repositories. Reanalysis and integration of themed collections from these studies may provide new insights, but requires further human curation. Here we report a crowdsourcing project to annotate and reanalyse a large number of gene expression profiles from Gene Expression Omnibus (GEO). Through a massive open online course on Coursera, over 70 participants from over 25 countries identify and annotate 2,460 single-gene perturbation signatures, 839 disease versus normal signatures, and 906 drug perturbation signatures. All these signatures are unique and are manually validated for quality. Global analysis of these signatures confirms known associations and identifies novel associations between genes, diseases and drugs. The manually curated signatures are used as a training set to develop classifiers for extracting similar signatures from the entire GEO repository. We develop a web portal to serve these signatures for query, download and visualization.
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| 7. |
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| 8. |
- Jafari, Rouhollah, et al.
(författare)
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Quench dynamics and zero-energy modes: The case of the Creutz model
- 2019
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Ingår i: Physical Review B. - 2469-9950. ; 99:5
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Tidskriftsartikel (refereegranskat)abstract
- In most lattice models, the closing of a band gap typically occurs at high-symmetry points in the Brillouin zone. Differently, in the Creutz model-describing a system of spinless fermions hopping on a two-leg ladder pierced by a magnetic field-the gap closing at the quantum phase transition between the two topologically nontrivial phases of the model can be moved by tuning the hopping amplitudes. We take advantage of this property to examine the nonequilibrium dynamics of the model after a sudden quench of the magnetic flux through the plaquettes of the ladder. For a quench to one of the equilibrium quantum critical points, we find that the revival period of the Loschmidt echo-measuring the overlap between initial and time-evolved states-is controlled by the gap closing zero-energy modes. In particular, and contrary to expectations, the revival period of the Loschmidt echo for a finite ladder does not scale linearly with size but exhibits jumps determined by the presence or absence of zero-energy modes. We further investigate the conditions for the appearance of dynamical quantum phase transitions in the model and find that, for a quench to an equilibrium critical point, such transitions occur only for ladders of sizes which host zero-energy modes. Exploiting concepts from quantum thermodynamics, we show that the average work and the irreversible work per lattice site exhibit a weak dependence on the size of the system after a quench across an equilibrium critical point, suggesting that quenching into a different phase induces effective correlations among the particles.
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| 9. |
- Jafari, Rouhollah, et al.
(författare)
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Real Space Renormalization of Majorana Fermions in Quantum Nano-Wire Superconductors
- 2017
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Ingår i: Journal of the Physical Society of Japan. - : Physical Society of Japan. - 0031-9015 .- 1347-4073. ; 86:2
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Tidskriftsartikel (refereegranskat)abstract
- We develop the real space quantum renormalization group (QRG) approach for majorana fermions. As an example we focus on the Kitaev chain to investigate the topological quantum phase transition (TQPT) in the one-dimensional spinless p-wave superconductor. Studying the behaviour of local compressibility and ground-state fidelity, show that the TQPT is signalled by the maximum of local compressibility at the quantum critical point tuned by the chemical potential. Moreover, a sudden drop of the ground-state fidelity and the divergence of fidelity susceptibility at the topological quantum critical point are used as proper indicators for the TQPT, which signals the appearance of Majorana fermions. Finally, we present the scaling analysis of ground-state fidelity near the critical point that manifests the universal information about the TQPT, which reveals two different scaling behaviors as we approach the critical point and thermodynamic limit.
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