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- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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- Pan, YX, et al.
(författare)
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The apolipoprotein B and apolipoprotein A-I Ratio serves as a strong prognostic factor for the overall survival of patients with colorectal cancer
- 2023
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Ingår i: Frontiers in oncology. - : Frontiers Media SA. - 2234-943X. ; 12, s. 1089688-
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Tidskriftsartikel (refereegranskat)abstract
- The lipid metabolism status of patients with colorectal cancer (CRC) has not been understood comprehensively. The present study investigated the characteristics of lipid metabolism parameters in CRC patients with or without metastases and identified the independent prognostic factors of long-term prognosis.MethodsThe clinicopathological data of 231 CRC patients along with 259 formalin-fixed paraffin-embedded samples with or without liver or lung metastasis were retrieved and stained for apolipoprotein B (apoB) via immunohistochemistry (IHC) in our center. The correlation and multivariable analysis between blood circulating apolipoprotein A-I (apoA1), apoB and overall survival (OS) were analyzed.ResultsIn the multivariable analysis, apoA1, apoB and apolipoprotein B and apolipoprotein A-I (apoB/A) ratio, were identified as independent prognostic factors for OS. Moreover, the apoB/A ratio showed a significantly negative association with OS time (R=-0.187, P=0.004). CRC patients with low apoB/A ratio had better 1-, 3- and 5-year OS rates than those who had high apoB/A ratio (87.1%, 54.3%, and 37.1% vs. 92.5%, 72.0%, and 59.5%, respectively, P=0.001). On histological level, similar expression intensity of apoB between primary CRC and liver metastases indicated better prognostic outcomes than those with different expression levels (100%, 83.3%, and 77.8% vs. 100%, 66.7%, and 33.3%, respectively; P=0.033). Higher level of apoB in the primary CRC interprets into increased incidence of liver metastases. However, the apoB expression levels in the CRC tumor were not parallel to the circulating lipid metabolism parameters.ConclusionsThe apoB/A ratio was a reliable independent prognostic factor for predicting the long-term OS of CRC patients. Moreover, the IHC of the primary CRC and metastatic lesions verified the metastatic potential of apoB through a different aspect. Lipid metabolism status for cancer progression reported in the present study possessed potentially prognostic value, but bench-scale studies are needed for their future clinical applications.
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- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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- Lam, BYK, et al.
(författare)
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The global burden of cerebral small vessel disease in low- and middle-income countries: A systematic review and meta-analysis
- 2023
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Ingår i: International journal of stroke : official journal of the International Stroke Society. - : SAGE Publications. - 1747-4949. ; 18:1, s. 15-27
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Tidskriftsartikel (refereegranskat)abstract
- Cerebral small vessel disease (cSVD) is a major cause of stroke and dementia. Previous studies on the prevalence of cSVD are mostly based on single geographically defined cohorts in high-income countries. Studies investigating the prevalence of cSVD in low- and middle-income countries (LMICs) are expanding but have not been systematically assessed. Aim: This study aims to systematically review the prevalence of cSVD in LMICs. Results: Articles were searched from the Ovid MEDLINE and EMBASE databases from 1 January 2000 to 31 March 2022, without language restrictions. Title/abstract screening, full-text review, and data extraction were performed by two to seven independent reviewers. The prevalence of cSVD and study sample size were extracted by pre-defined world regions and health status. The Risk of Bias for Non-randomized Studies tool was used. The protocol was registered on PROSPERO (CRD42022311133). A meta-analysis of proportion was performed to assess the prevalence of different magnetic resonance imaging markers of cSVD, and a meta-regression was performed to investigate associations between cSVD prevalence and type of study, age, and male: female ratio. Of 2743 studies identified, 42 studies spanning 12 global regions were included in the systematic review. Most of the identified studies were from China (n = 23). The median prevalence of moderate-to-severe white matter hyperintensities (WMHs) was 20.5%, 40.5%, and 58.4% in the community, stroke, and dementia groups, respectively. The median prevalence of lacunes was 0.8% and 33.5% in the community and stroke groups. The median prevalence of cerebral microbleeds (CMBs) was 10.7% and 22.4% in the community and stroke groups. The median prevalence of moderate-to-severe perivascular spaces was 25.0% in the community. Meta-regression analyses showed that the weighted median age (51.4 ± 0.0 years old; range: 36.3–80.2) was a significant predictor of the prevalence of moderate-to-severe WMH and lacunes, while the type of study was a significant predictor of the prevalence of CMB. The heterogeneity of studies was high (>95%). Male participants were overrepresented. Conclusions: This systematic review and meta-analysis provide data on cSVD prevalence in LMICs and demonstrated the high prevalence of the condition. cSVD research in LMICs is being published at an increasing rate, especially between 2010 and 2022. More data are particularly needed from Sub-Saharan Africa and Central Europe, Eastern Europe, and Central Asia.
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| 22. |
- Lin, SC, et al.
(författare)
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A Natural Botanical Product, Resveratrol, Effectively Suppresses Vesicular Stomatitis Virus Infection In Vitro
- 2021
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Ingår i: Plants (Basel, Switzerland). - : MDPI AG. - 2223-7747. ; 10:6
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Tidskriftsartikel (refereegranskat)abstract
- Numerous natural phytochemicals such as resveratrol are acknowledged as potent botanical agents in regulating immune responses. However, it is less understood whether such immunomodulatory phytochemicals are appropriate for use as direct treatments in veterinary viral diseases. In the present study, we investigated the efficacy of resveratrol in suppressing vesicular stomatitis virus (VSV) infection. Outbreaks of VSV can cause massive economic loss in poultry and livestock husbandry farming, and VSV treatment is in need of therapeutic development. We utilized a recombinant VSV that expresses green fluorescent protein (GFP) to measure viral replication in cells treated with resveratrol. Our findings revealed that resveratrol treatment affords a protective effect, shown by increased viability and reduced viral replication, as indicated by a reduction in fluorescent signals. Additionally, we found that resveratrol inhibition of VSV infection occurs via suppression of the caspase cascade. Structural analysis also indicated that resveratrol potentially interacts with the active sites of caspase-3 and -7, facilitating antiviral activity. The potential effect of resveratrol on reducing VSV infection in vitro suggests that resveratrol should be further investigated as a potential veterinary therapeutic or prophylactic agent.
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- Niemi, MEK, et al.
(författare)
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- 2021
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