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Sökning: L773:0007 0920 OR L773:1532 1827 > (2015-2019)

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1.
  • Bamia, C., et al. (författare)
  • Fruit and vegetable consumption in relation to hepatocellular carcinoma in a multi-centre, European cohort study
  • 2015
  • Ingår i: British Journal of Cancer. - 0007-0920 .- 1532-1827. ; 112:7, s. 1273-1282
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Background:Vegetable and/or fruit intakes in association with hepatocellular carcinoma (HCC) risk have been investigated in case-control studies conducted in specific European countries and cohort studies conducted in Asia, with inconclusive results. No multi-centre European cohort has investigated the indicated associations. Methods: In 486 799 men/women from the European Prospective Investigation into Cancer and nutrition, we identified 201 HCC cases after 11 years median follow-up. We calculated adjusted hazard ratios (HRs) for HCC incidence for sex-specific quintiles and per 100 g d(-1) increments of vegetable/fruit intakes. Results: Higher vegetable intake was associated with a statistically significant, monotonic reduction of HCC risk: HR (100 g d(-1) increment): 0.83; 95% CI: 0.71-0.98. This association was consistent in sensitivity analyses with no apparent heterogeneity across strata of HCC risk factors. Fruit intake was not associated with HCC incidence: HR (100 g d(-1) increment): 1.01; 95% CI: 0.92-1.11. Conclusions: Vegetable, but not fruit, intake is associated with lower HCC risk with no evidence for heterogeneity of this association in strata of important HCC risk factors. Mechanistic studies should clarify pathways underlying this association. Given that HCC prognosis is poor and that vegetables are practically universally accessible, our results may be important, especially for those at high risk for the disease.</p>
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2.
  • Bellomo, Claudia, et al. (författare)
  • Transforming growth factor beta as regulator of cancer stemness and metastasis
  • 2016
  • Ingår i: British Journal of Cancer. - 0007-0920 .- 1532-1827. ; 115:7, s. 761-769
  • Forskningsöversikt (refereegranskat)abstract
    • <p>Key elements of cancer progression towards metastasis are the biological actions of cancer stem cells and stromal cells in the tumour microenvironment. Cross-communication between tumour and stromal cells is mediated by secreted cytokines, one of which, the transforming growth factor beta (TGF beta), regulates essentially every cell within the malignant tissue. In this article, we focus on the actions of TGF beta on cancer stem cells, cancer-associated fibroblasts and immune cells that assist the overall process of metastatic dissemination. We aim at illustrating intricate connections made by various cells in the tumour tissue and which depend on the action of TGF beta.</p>
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3.
  • Besevic, Jelena, et al. (författare)
  • Reproductive factors and epithelial ovarian cancer survival in the EPIC cohort study
  • 2015
  • Ingår i: British Journal of Cancer. - Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 113:11, s. 1622-1631
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Background: Reproductive factors influence the risk of developing epithelial ovarian cancer (EOC), but little is known about their association with survival. We tested whether prediagnostic reproductive factors influenced EOC-specific survival among 1025 invasive EOC cases identified in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, which included 521 330 total participants (approximately 370 000 women) aged 25-70 years at recruitment from 1992 to 2000. Methods: Information on reproductive characteristics was collected at recruitment. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), and multivariable models were adjusted for age and year of diagnosis, body mass index, tumour stage, smoking status and stratified by study centre. Results: After a mean follow-up of 3.6 years (+/- 3.2 s.d.) following EOC diagnosis, 511 (49.9%) of the 1025 women died from EOC. We observed a suggestive survival advantage in menopausal hormone therapy (MHT) users (ever vs never use, HR = 0.80, 95% CI = 0.62-1.03) and a significant survival benefit in long-term MHT users (&gt;= 5 years use vs never use, HR = 0.70, 95% CI = 0.50-0.99, P-trend = 0.04). We observed similar results for MHT use when restricting to serous cases. Other reproductive factors, including parity, breastfeeding, oral contraceptive use and age at menarche or menopause, were not associated with EOC-specific mortality risk. Conclusions: Further studies are warranted to investigate the possible improvement in EOC survival in MHT users.</p>
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4.
  • Bjørge, Tone, et al. (författare)
  • Reproductive history and risk of colorectal adenocarcinoma in parous women a Nordic population-based case-control study
  • 2016
  • Ingår i: British Journal of Cancer. - 0007-0920 .- 1532-1827. ; 115:11, s. 1416-1420
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Background: Data are conflicting regarding the role of endogenous sex hormones in colorectal carcinogenesis. In this large population-based study, we pooled data from birth and cancer registries in four Nordic countries, to evaluate the risk of colorectal adenocarcinoma in relation to women's reproductive history. Methods: We conducted a population-based case-control study among women registered in Nordic birth registries. The study included colorectal adenocarcinoma cases diagnosed in Denmark, Finland, Norway, and Sweden during 1967-2013 and up to 10 matched controls per case, in total 22 185 cases and 220 246 controls. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were derived from conditional logistic regression models. We had limited information available on possible confounders. Results: We found no evidence for associations between colorectal adenocarcinoma and parity, age at first and last birth, and time since first and last birth. The risk estimates were also close to unity for specific cancer subsites (proximal and distal colon and rectum). As well, when the analyses were stratified on menopausal status, parity, and mother's year of birth, no indication of associations was found. Conclusions: In this large, Nordic population-based study, no evidence for associations was found between women's reproductive history and colorectal adenocarcinoma in parous women.</p>
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5.
  • Bogdanovic, G, et al. (författare)
  • Virome characterisation from Guthrie cards in children who later developed acute lymphoblastic leukaemia.
  • 2016
  • Ingår i: British Journal of Cancer. - 0007-0920 .- 1532-1827. ; 115:8, s. 1008-1014
  • Tidskriftsartikel (refereegranskat)abstract
    • <p><strong>BACKGROUND:</strong> Some childhood acute lymphoblastic leukaemias (ALL) can be traced back to a prenatal origin, where a virus infection could be involved in the first pre-leukaemic clone development. The DNA virome of 95 children who later developed ALL was characterised from neonatal blood spots (NBS) using unbiased next-generation sequencing (NGS) and compared with the virome of 95 non-ALL controls.</p><p><strong>METHODS:</strong> DNA was individually extracted from the ALL-patients and controls, pooled, randomly amplified and sequenced using the Illumina MiSeq Sequencing System.</p><p><strong>RESULTS:</strong> Virus-like sequences identified in both groups mapped to human endogenous retroviruses and propionibacterium phage, considered a part of the normal microbial flora. Potential pathogens human herpesvirus type 6 (HHV-6) and parvovirus B19 were also identified, but only few samples in both ALL and controls tested positive by PCR follow-up.</p><p><strong>CONCLUSIONS:</strong> Unbiased NGS was employed to search for DNA from potential infectious agents in neonatal samples of children who later developed ALL. Although several viral candidates were identified in the NBS samples, further investigation by PCR suggested that these viruses did not have a major role in ALL development.</p>
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6.
  • Boldrup, Linda, et al. (författare)
  • Downregulation of miRNA-424 : a sign of field cancerisation in clinically normal tongue adjacent to squamous cell carcinoma
  • 2015
  • Ingår i: British Journal of Cancer. - Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 112:11, s. 1760-1765
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Background: The overall survival for patients with squamous cell carcinoma of the tongue is low and the search for early diagnostic and prognostic markers is thus essential. MicroRNAs have been suggested as potential prognostic and diagnostic candidates in squamous cell carcinoma of head and neck in general. Methods: On the basis of the known differences between sub-sites within the oral cavity, we investigated the expression and role of microRNA-424 in squamous cell carcinoma arising in tongue. MicroRNA levels were measured by qRT-PCR in both tissue and plasma samples. Results: Levels of microRNA-424 were upregulated in tongue squamous cell carcinoma, but not in tumours originating from gingiva or floor of the mouth. Interestingly, microRNA-424 was downregulated in clinically normal tongue tissue next to tumour compared with completely healthy tongue, indicating that microRNA-424 could be a marker of field cancerisation in this tumour type. However, expression of microRNA-424 in a tongue-derived epithelial cell line revealed no significant changes in the expression profile of proteins and genes. Conclusions: Our patient data show that microRNA-424 alterations are a marker of field cancerisation specific for tongue tumourigenesis, which also could have a role in development of tongue squamous cell carcinoma.</p>
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7.
  • Boldrup, L., et al. (författare)
  • Downregulation of miRNA-424 : a sign of field cancerisation in clinically normal tongue adjacent to squamous cell carcinoma
  • 2015
  • Ingår i: British Journal of Cancer. - 0007-0920 .- 1532-1827. ; 112:11, s. 1760-1765
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Background: The overall survival for patients with squamous cell carcinoma of the tongue is low and the search for early diagnostic and prognostic markers is thus essential. MicroRNAs have been suggested as potential prognostic and diagnostic candidates in squamous cell carcinoma of head and neck in general. Methods: On the basis of the known differences between sub-sites within the oral cavity, we investigated the expression and role of microRNA-424 in squamous cell carcinoma arising in tongue. MicroRNA levels were measured by qRT-PCR in both tissue and plasma samples. Results: Levels of microRNA-424 were upregulated in tongue squamous cell carcinoma, but not in tumours originating from gingiva or floor of the mouth. Interestingly, microRNA-424 was downregulated in clinically normal tongue tissue next to tumour compared with completely healthy tongue, indicating that microRNA-424 could be a marker of field cancerisation in this tumour type. However, expression of microRNA-424 in a tongue-derived epithelial cell line revealed no significant changes in the expression profile of proteins and genes. Conclusions: Our patient data show that microRNA-424 alterations are a marker of field cancerisation specific for tongue tumourigenesis, which also could have a role in development of tongue squamous cell carcinoma.</p>
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8.
  • Brodin, Bertha A., et al. (författare)
  • Drug sensitivity testing on patient-derived sarcoma cells predicts patient response to treatment and identifies c-Sarc inhibitors as active drugs for translocation sarcomas
  • 2019
  • Ingår i: British Journal of Cancer. - 0007-0920 .- 1532-1827. ; 120:4, s. 435-443
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>BACKGROUND: Heterogeneity and low incidence comprise the biggest challenge in sarcoma diagnosis and treatment. Chemotherapy, although efficient for some sarcoma subtypes, generally results in poor clinical responses and is mostly recommended for advanced disease. Specific genomic aberrations have been identified in some sarcoma subtypes but few of them can be targeted with approved drugs. METHODS: We cultured and characterised patient-derived sarcoma cells and evaluated their sensitivity to 525 anti-cancer agents including both approved and non-approved drugs. In total, 14 sarcomas and 5 healthy mesenchymal primary cell cultures were studied. The sarcoma biopsies and derived cells were characterised by gene panel sequencing, cancer driver gene expression and by detecting specific fusion oncoproteins in situ in sarcomas with translocations. RESULTS: Soft tissue sarcoma cultures were established from patient biopsies with a success rate of 58%. The genomic profile and drug sensitivity testing on these samples helped to identify targeted inhibitors active on sarcomas. The cSrc inhibitor Dasatinib was identified as an active drug in sarcomas carrying chromosomal translocations. The drug sensitivity of the patient sarcoma cells ex vivo correlated with the response to the former treatment of the patient. CONCLUSIONS: Our results show that patient-derived sarcoma cells cultured in vitro are relevant and practical models for genotypic and phenotypic screens aiming to identify efficient drugs to treat sarcoma patients with poor treatment options.</p>
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9.
  • Charitou, Theodosia, et al. (författare)
  • Transcriptional and metabolic rewiring of colorectal cancer cells expressing the oncogenic KRAS(G13D) mutation
  • 2019
  • Ingår i: British Journal of Cancer. - NATURE PUBLISHING GROUP. - 0007-0920 .- 1532-1827. ; 121:1, s. 37-50
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>BACKGROUND: Activating mutations in KRAS frequently occur in colorectal cancer (CRC) patients, leading to resistance to EGFRtargeted therapies. METHODS: To better understand the cellular reprogramming which occurs in mutant KRAS cells, we have undertaken a systems-level analysis of four CRC cell lines which express either wild type (wt) KRAS or the oncogenic KRAS(G13D) allele (mtKRAS). RESULTS: RNAseq revealed that genes involved in ribosome biogenesis, mRNA translation and metabolism were significantly upregulated in mtKRAS cells. Consistent with the transcriptional data, protein synthesis and cell proliferation were significantly higher in the mtKRAS cells. Targeted metabolomics analysis also confirmed the metabolic reprogramming in mtKRAS cells. Interestingly, mtKRAS cells were highly transcriptionally responsive to EGFR activation by TGF alpha stimulation, which was associated with an unexpected downregulation of genes involved in a range of anabolic processes. While TGF alpha treatment strongly activated protein synthesis in wtKRAS cells, protein synthesis was not activated above basal levels in the TGF alpha-treated mtKRAS cells. This was likely due to the defective activation of the mTORC1 and other pathways by TGF alpha in mtKRAS cells, which was associated with impaired activation of PKB signalling and a transient induction of AMPK signalling. CONCLUSIONS: We have found that mtKRAS cells are substantially rewired at the transcriptional, translational and metabolic levels and that this rewiring may reveal new vulnerabilities in oncogenic KRAS CRC cells that could be exploited in future.</p>
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10.
  • Claassen, Yvette H. M., et al. (författare)
  • Treatment and survival of rectal cancer patients over the age of 80 years : a EURECCA international comparison
  • 2018
  • Ingår i: British Journal of Cancer. - Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 119:4, s. 517-522
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>BACKGROUND: The optimal treatment strategy for older rectal cancer patients remains unclear. The current study aimed to compare treatment and survival of rectal cancer patients aged 80+.</p><p>METHODS: Patients of &gt;= 80 years diagnosed with rectal cancer between 2001 and 2010 were included. Population-based cohorts from Belgium (BE), Denmark (DK), the Netherlands (NL), Norway (NO) and Sweden (SE) were compared side by side for neighbouring countries on treatment strategy and 5-year relative survival (RS), adjusted for sex and age. Analyses were performed separately for stage I-III patients and stage IV patients.</p><p>RESULTS: Overall, 19 634 rectal cancer patients were included. For stage I-III patients, 5-year RS varied from 61.7% in BE to 72.3% in SE. Proportion of preoperative radiotherapy ranged between 7.9% in NO and 28.9% in SE. For stage IV patients, 5-year RS differed from 2.8% in NL to 5.6% in BE. Rate of patients undergoing surgery varied from 22.2% in DK to 40.8% in NO.</p><p>CONCLUSIONS: Substantial variation was observed in the 5-year relative survival between European countries for rectal cancer patients aged 80+, next to a wide variation in treatment, especially in the use of preoperative radiotherapy in stage I-III patients and in the rate of patients undergoing surgery in stage IV patients.</p>
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