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

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  • Heikkila, Katriina, et al. (författare)
  • Long working hours and cancer risk a multi-cohort study
  • 2016
  • Ingår i: British Journal of Cancer. - 0007-0920 .- 1532-1827. ; 114:7, s. 813-818
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Background: Working longer than the maximum recommended hours is associated with an increased risk of cardiovascular disease, but the relationship of excess working hours with incident cancer is unclear. Methods: This multi-cohort study examined the association between working hours and cancer risk in 116 462 men and women who were free of cancer at baseline. Incident cancers were ascertained from national cancer, hospitalisation and death registers; weekly working hours were self-reported. Results: During median follow-up of 10.8 years, 4371 participants developed cancer (n colorectal cancer: 393; n lung cancer: 247; n breast cancer: 833; and n prostate cancer: 534). We found no clear evidence for an association between working hours and the overall cancer risk. Working hours were also unrelated the risk of incident colorectal, lung or prostate cancers. Working &gt;= 55 h per week was associated with 1.60-fold (95% confidence interval 1.12-2.29) increase in female breast cancer risk independently of age, socioeconomic position, shift-and night-time work and lifestyle factors, but this observation may have been influenced by residual confounding from parity. Conclusions: Our findings suggest that working long hours is unrelated to the overall cancer risk or the risk of lung, colorectal or prostate cancers. The observed association with breast cancer would warrant further research.</p>
  • Hilborn, Erik, et al. (författare)
  • Androgen receptor expression predicts beneficial tamoxifen response in oestrogen receptor-alpha-negative breast cancer
  • 2016
  • Ingår i: British Journal of Cancer. - NATURE PUBLISHING GROUP. - 0007-0920 .- 1532-1827. ; 114:3, s. 248-255
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Background: Although the androgen receptor (AR) is frequently expressed in breast cancer, its relevance in the disease is not fully understood. In addition, the relevance of AR in determining tamoxifen treatment efficiency requires evaluation. Purpose: To investigate the tamoxifen predictive relevance of the AR protein expression in breast cancer. Methods Patients were randomised to tamoxifen 40 mg daily for 2 or 5 years or to no endocrine treatment. Mean follow-up was 15 years. Hazard ratios were calculated with recurrence-free survival as end point. Results: In patients with oestrogen receptor (ER)-negative tumours, expression of AR predicted decreased recurrence rate with tamoxifen (hazard ratio (HR) = 0.34; 95% confidence interval (CI) = 0.14-0.81; P = 0.015), whereas the opposite was seen in the AR- group (HR = 2.92; 95% CI = 1.16-7.31; P = 0.022). Interaction test was significant P &amp;lt; 0.001. Patients with triple-negative and AR+ tumours benefitted from tamoxifen treatment (HR = 0.12; 95% CI = 0.014-0.95 P = 0.044), whereas patients with AR- tumours had worse outcome when treated with tamoxifen (HR = 3.98; 95% CI = 1.32-12.03; P = 0.014). Interaction test was significant P = 0.003. Patients with ER+ tumours showed benefit from tamoxifen treatment regardless of AR expression. Conclusions: AR can predict tamoxifen treatment benefit in patients with ER- tumours and triple-negative breast cancer.</p>
  • Li, K., et al. (författare)
  • An epidemiologic risk prediction model for ovarian cancer in Europe : the EPIC study
  • 2015
  • Ingår i: British Journal of Cancer. - 0007-0920 .- 1532-1827. ; 112:7, s. 1257-1265
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Background: Ovarian cancer has a high case-fatality ratio, largely due to late diagnosis. Epidemiologic risk prediction models could help identify women at increased risk who may benefit from targeted prevention measures, such as screening or chemopreventive agents. Methods: We built an ovarian cancer risk prediction model with epidemiologic risk factors from 202 206 women in the European Prospective Investigation into Cancer and Nutrition study. Results: Older age at menopause, longer duration of hormone replacement therapy, and higher body mass index were included as increasing ovarian cancer risk, whereas unilateral ovariectomy, longer duration of oral contraceptive use, and higher number of full-term pregnancies were decreasing risk. The discriminatory power (overall concordance index) of this model, as examined with five-fold cross-validation, was 0.64 (95% confidence interval (CI): 0.57, 0.70). The ratio of the expected to observed number of ovarian cancer cases occurring in the first 5 years of follow-up was 0.90 (293 out of 324, 95% CI: 0.81-1.01), in general there was no evidence for miscalibration. Conclusion: Our ovarian cancer risk model containing only epidemiological data showed modest discriminatory power for a Western European population. Future studies should consider adding informative biomarkers to possibly improve the predictive ability of the model.</p>
  • Lindemann, Kristina, et al. (författare)
  • Chemotherapy vs tamoxifen in platinum-resistant ovarian cancer: a phase III, randomised, multicentre trial (Ovaresist)
  • 2017
  • Ingår i: British Journal of Cancer. - NATURE PUBLISHING GROUP. - 0007-0920 .- 1532-1827. ; 116:4, s. 455-463
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Background: Chemotherapy in platinum-resistant ovarian cancer (PROC) aims for palliation and prolonging of progression-free survival (PFS). This study compares Health-related Quality of Life (HRQoL) and efficacy between single-agent chemotherapy and tamoxifen in PROC. Methods: Patients with PROC were randomised (2 : 1) to chemotherapy (weekly paclitaxel 80 mg m(-2) or four weekly pegylated liposomal doxorubicin 40 mg m(-2)) or tamoxifen 40mg daily. The primary end point was HRQoL. Secondary end points were PFS by RECIST and overall survival (OS). Results: Between March 2002 and December 2007, 156 and 82 patients were randomised to chemotherapy and tamoxifen, respectively. In the chemotherapy arm, a significantly larger proportion of patients experienced a worsening in their social functioning. There was no difference in the proportion of patients experiencing improvement of gastrointestinal symptoms. Median PFS on tamoxifen was 8.3 weeks (95% CI, 8.0-10.4) compared with 12.7 weeks (95% CI, 9.0-16.3) on chemotherapy (HR, 1.54; 95% CI, 1.16-2.05; log-rank P = 0.003). There was no difference in OS between the treatment arms. Conclusions: Patients on chemotherapy had longer PFS but experienced more toxicity and poorer HRQoL compared with tamoxifen. Control over gastrointestinal symptoms was not better on chemotherapy. These data are important for patient counselling and highlight the need to incorporate HRQoL end points in studies of PROC.</p>
  • Lophatananon, Artitaya, et al. (författare)
  • Height, selected genetic markers and prostate cancer risk : results from the PRACTICAL consortium.
  • 2017
  • Ingår i: British Journal of Cancer. - 0007-0920 .- 1532-1827. ; 117:5, s. 734-743
  • Tidskriftsartikel (refereegranskat)abstract
    • <p><strong>BACKGROUND:</strong> Evidence on height and prostate cancer risk is mixed, however, recent studies with large data sets support a possible role for its association with the risk of aggressive prostate cancer.</p><p><strong>METHODS:</strong> We analysed data from the PRACTICAL consortium consisting of 6207 prostate cancer cases and 6016 controls and a subset of high grade cases (2480 cases). We explored height, polymorphisms in genes related to growth processes as main effects and their possible interactions.</p><p><strong>RESULTS:</strong> The results suggest that height is associated with high-grade prostate cancer risk. Men with height &gt;180 cm are at a 22% increased risk as compared to men with height &lt;173 cm (OR 1.22, 95% CI 1.01-1.48). Genetic variants in the growth pathway gene showed an association with prostate cancer risk. The aggregate scores of the selected variants identified a significantly increased risk of overall prostate cancer and high-grade prostate cancer by 13% and 15%, respectively, in the highest score group as compared to lowest score group.</p><p><strong>CONCLUSIONS:</strong> There was no evidence of gene-environment interaction between height and the selected candidate SNPs.Our findings suggest a role of height in high-grade prostate cancer. The effect of genetic variants in the genes related to growth is seen in all cases and high-grade prostate cancer. There is no interaction between these two exposures.</p>
  • Loskog, Angelica, et al. (författare)
  • Immunostimulatory AdCD40L gene therapy combined with low-dose cyclophosphamide in metastatic melanoma patients
  • 2016
  • Ingår i: British Journal of Cancer. - 0007-0920 .- 1532-1827. ; 114:8, s. 872-880
  • Tidskriftsartikel (refereegranskat)abstract
    • <p><strong>BACKGROUND:</strong> Current approaches for treating metastatic malignant melanoma (MM) are not effective enough and are associated with serious adverse events. Due to its immunogenicity, melanoma is an attractive target for immunostimulating therapy. In this phase I/IIa study, local AdCD40L immunostimulatory gene therapy was evaluated in patients with MM.</p><p><strong>METHODS:</strong> AdCD40L is an adenovirus carrying the gene for CD40 ligand. Patients that failed standard treatments were enrolled. Six patients received four weekly intratumoral AdCD40L injections. Next, nine patients received low-dose cyclophosphamide conditioning before the first and fourth AdCD40L injection. The blood samples were collected at multiple time points for chemistry, haematology and immunology evaluations. Radiology was performed at enrolment and repeated twice after the treatment.</p><p><strong>RESULTS:</strong> AdCD40L was safe with mild transient reactions. No objective responses were recorded by MRI, however, local and distant responses were seen on FDG-PET. The overall survival at 6 months was significantly better when cyclophosphamide was added to AdCD40L. The patients with the best survival developed the highest levels of activated T cells and experienced a pronounced decrease of intratumoral IL8.</p><p><strong>CONCLUSIONS:</strong> AdCD40L therapy for MM was well tolerated. Local and distant responses along with better survival in the low-dose cyclophosphamide group are encouraging.</p>
  • Martikainen, Miika, et al. (författare)
  • Oncolytic alphavirus SFV-VA7 efficiently eradicates subcutaneous and orthotopic human prostate tumours in mice
  • 2017
  • Ingår i: British Journal of Cancer. - NATURE PUBLISHING GROUP. - 0007-0920 .- 1532-1827. ; 117:1, s. 51-55
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Background: Despite recent therapeutic and diagnostic advances, prostate cancer remains the second leading cause of cancer-related deaths among men in the Western world. Oncolytic viruses that replicate selectively in tumour cells represent a novel treatment candidate for these malignancies.</p><p>Methods: We analysed infectivity of avirulent Semliki Firest virus SFV-VA7 in human prostate cancer cell lines VCaP, LNCaP and 22Rv1 and in nonmalignant prostate epithelial cell line RWPE-1. Therapeutic potency of SFV-VA7 was evaluated in subcutaneous and orthotopic mouse LNCaP xenograft models.</p><p>Results: SFV-VA7 infected and killed the tested human prostate cancer cell lines irrespective of their hormone response status, while the nonmalignant prostate epithelial cell line RWPE-1 proved highly virus resistant. Notably, a single peritoneal dose of SFV-VA7 was sufficient to eradicate all subcutaneous and orthotopic LNCaP tumours.</p><p>Conclusions: Our results indicate that SFV-VA7 is a novel, promising therapeutic virus against prostate cancer warranting further testing in early clinical trials.</p>
  • Melvin, Jennifer C., et al. (författare)
  • Progression of breast cancer following locoregional ipsilateral recurrence : importance of interval time
  • 2016
  • Ingår i: British Journal of Cancer. - 0007-0920 .- 1532-1827. ; 114:1, s. 88-95
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Background: Studies comparing prognosis of breast cancer (BC) patients with and without locoregional recurrence (LR) present conflicting results. We aimed to improve our understanding of the impact of LR on prognosis by examining a large cohort of patients treated at Guy's and St Thomas' NHS Foundation Trust. Methods: Risk factors associated with BC-specific death were investigated using Cox proportional hazards regression in 5199 women diagnosed between 1975 and 2007. Breast cancer-specific death following LR was assessed with Poisson regression. Results: Overall, 552 women (11%) developed LR, with a median follow-up time of 4.28 years. Known factors associated with BC-specific death (tumour stage, grade, and nodal status) were of significance in our data. Women with a shorter disease-free interval had a worse prognosis. For instance, the HR for BC-specific death among women undergoing mastectomy with an LR 0.5-1 year after diagnosis of their primary tumour was 6.67 (95% CI: 3.71-11.99), when compared with women who did not experience LR. Conclusions: It often remains difficult to distinguish between a genuine LR and a new primary. The HRs for risk of BC-specific death following a second lesion suggest that they may act as a marker of systemic disease, large tumour burden, or depleted host defence. The clinically highly relevant impairment in prognosis calls for further research into the underlying mechanisms. We showed that for at least 15 years of follow-up, the prognosis in women following the occurrence of an LR may benefit from careful diagnostic and therapeutic management.</p>
  • Mezheyeuski, Artur, et al. (författare)
  • Stroma-normalised vessel density predicts benefit from adjuvant fluorouracil-based chemotherapy in patients with stage II/III colon cancer
  • 2019
  • Ingår i: British Journal of Cancer. - NATURE PUBLISHING GROUP. - 0007-0920 .- 1532-1827. ; 121:4, s. 303-311
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>BACKGROUND: Identification of biomarkers associated with benefit of adjuvant chemotherapy in stage II/III colon cancer is an important task. METHODS: Vessel density (VD) and tumour stroma were analysed in a randomised-trial-derived discovery cohort (n = 312) and in a stage II/III group of a population-based validation cohort (n = 85). VD was scored separately in the tumour centre, invasive margin and peritumoral stroma compartments and quantitated as VD/total analysed tissue area or VD/stroma area. RESULTS: High stroma-normalised VD in the invasive margin was associated with significantly longer time to recurrence and overall survival (OS) (p = 0.002 and p = 0.006, respectively) in adjuvant-treated patients of the discovery cohort, but not in surgery-only patients. Stroma-normalised VD in the invasive margin and treatment effect were significantly associated according to a formal interaction test (p = 0.009). Similarly, in the validation cohort, high stroma-normalised VD was associated with OS in adjuvant-treated patients, although statistical significance was not reached (p = 0.051). CONCLUSION: Through the use of novel digitally scored vessel-density-related metrics, this exploratory study identifies stroma-normalised VD in the invasive margin as a candidate marker for benefit of adjuvant 5-FU-based chemotherapy in stage II/III colon cancer. The findings, indicating particular importance of vessels in the invasive margin, also suggest biological mechanisms for further exploration.</p>
  • Molina-Montes, Esther, et al. (författare)
  • Mediterranean diet and risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition cohort
  • 2017
  • Ingår i: British Journal of Cancer. - 0007-0920 .- 1532-1827. ; 116:6, s. 811-820
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Background: The Mediterranean diet (MD) has been proposed as a means for cancer prevention, but little evidence has been accrued regarding its potential to prevent pancreatic cancer. We investigated the association between the adherence to the MD and pancreatic cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.</p><p>Methods: Over half a million participants from 10 European countries were followed up for over 11 years, after which 865 newly diagnosed exocrine pancreatic cancer cases were identified. Adherence to the MD was estimated through an adapted score without the alcohol component (arMED) to discount alcohol-related harmful effects. Cox proportional hazards regression models, stratified by age, sex and centre, and adjusted for energy intake, body mass index, smoking status, alcohol intake and diabetes status at recruitment, were used to estimate hazard ratios (HRs) associated with pancreatic cancer and their corresponding 95% confidence intervals (CIs).</p><p>Results: Adherence to the arMED score was not associated with risk of pancreatic cancer (HR high<em>vs</em> low adherence=0.99; 95% CI: 0.77–1.26, and HR per increments of two units in adherence to arMED=1.00; 95% CI: 0.94–1.06). There was no convincing evidence for heterogeneity by smoking status, body mass index, diabetes or European region. There was also no evidence of significant associations in analyses involving microscopically confirmed cases, plausible reporters of energy intake or other definitions of the MD pattern.</p><p>Conclusions: A high adherence to the MD is not associated with pancreatic cancer risk in the EPIC study.</p>
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