| 1. |
- Frödin, Magnus, et al.
(författare)
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Perivascular PDGFR-β is an independent marker for prognosis in renal cell carcinoma
- 2017
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 116:2, s. 195-201
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Tidskriftsartikel (refereegranskat)abstract
- Background:Renal cell carcinoma (RCC) is a highly vascularised tumour, where anti-Angiogenic treatment with multi-Tyrosine-kinase-inhibitor, is used for first-line treatment of metastatic disease. Variations in vascular characteristics are likely to contribute to variations in intrinsic aggressiveness of the disease. Emerging studies are identifying perivascular status, including perivascular PDGFR-β, as a determinant of prognosis in other tumour types.Methods:This work explored the impact on prognosis of vascular characteristics in RCC through analyses of a population-based collection of tumours from surgery-Alone-Treated patients. The quantitative data from a panel of vascular metrics were obtained through computerised image analysis of sections double-stained for expression of the endothelial cell marker CD34 together with perivascular markers α-SMA or PDGFR-β.Results:Perivascular expression of PDGFR-β and α-SMA were positively correlated to each other, and negatively correlated to vessel density. High expression of PDGFR-β and α-SMA as well as low vessel density was significantly associated with short survival in uni-and multivariate analyses. Subgroup analyses demonstrated that the prognostic impact of the perivascular markers was particularly prominent in the T4-subgroup. A novel metric, related to PDGFR-β perivascular heterogeneity, was also associated with prognosis in uni-And multi-variate analyses. This novel metric also acted as a prognosis marker in ovarian cancer.Conclusions:The study demonstrates previously unrecognised associations between RCC survival and the absolute levels, and variability, of perivascular PDGFR-β. This marker should be further explored in other RCC cohorts. Findings also suggest mechanistic analyses and studies on the relationship between perivascular status and efficacy of multi-Tyrosine-kinase-inhibitors.
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| 2. |
- Heinonen, HR, et al.
(författare)
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Global metabolomic profiling of uterine leiomyomas
- 2017
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Ingår i: British journal of cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 117:12, s. 1855-1864
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Tidskriftsartikel (refereegranskat)
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| 3. |
- Molina-Montes, Esther, et al.
(författare)
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Mediterranean diet and risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition cohort
- 2017
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 116:6, s. 811-820
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Tidskriftsartikel (refereegranskat)abstract
- 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.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).Results:Adherence to the arMED score was not associated with risk of pancreatic cancer (HR high vs 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.Conclusions:A high adherence to the MD is not associated with pancreatic cancer risk in the EPIC study.
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| 4. |
- Stepien, Magdalena, et al.
(författare)
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Circulating copper and zinc levels and risk of hepatobiliary cancers in Europeans
- 2017
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 116:5, s. 688-696
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Copper and zinc are essential micronutrients and cofactors of many enzymatic reactions that may be involved in liver-cancer development. We aimed to assess pre-diagnostic circulating levels of copper, zinc and their ratio (Cu/Zn) in relation to hepatocellular carcinoma (HCC), intrahepatic bile duct (IHBD) and gall bladder and biliary tract (GBTC) cancers.METHODS: A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition cohort. Serum zinc and copper levels were measured in baseline blood samples by total reflection X-ray fluorescence in cancer cases (HCC n=106, IHDB n=34, GBTC n=96) and their matched controls (1:1). The Cu/Zn ratio, an indicator of the balance between the micronutrients, was computed. Multivariable adjusted odds ratios and 95% confidence intervals (OR; 95% CI) were used to estimate cancer risk.RESULTS: For HCC, the highest vs lowest tertile showed a strong inverse association for zinc (OR=0.36; 95% CI: 0.13-0.98, Ptrend=0.0123), but no association for copper (OR=1.06; 95% CI: 0.45-2.46, Ptrend=0.8878) in multivariable models. The calculated Cu/Zn ratio showed a positive association for HCC (OR=4.63; 95% CI: 1.41-15.27, Ptrend=0.0135). For IHBC and GBTC, no significant associations were observed.CONCLUSIONS: Zinc may have a role in preventing liver-cancer development, but this finding requires further investigation in other settings.
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| 5. |
- Fortner, Renée T., et al.
(författare)
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Anti-Mullerian hormone and endometrial cancer : a multi-cohort study
- 2017
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Ingår i: British Journal of Cancer. - : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 117:9, s. 1412-1418
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Tidskriftsartikel (refereegranskat)abstract
- Background: The Mullerian ducts are the embryological precursors of the female reproductive tract, including the uterus; anti-Mullerian hormone (AMH) has a key role in the regulation of foetal sexual differentiation. Anti-Mullerian hormone inhibits endometrial tumour growth in experimental models by stimulating apoptosis and cell cycle arrest. To date, there are no prospective epidemiologic data on circulating AMH and endometrial cancer risk. Methods: We investigated this association among women premenopausal at blood collection in a multicohort study including participants from eight studies located in the United States, Europe, and China. We identified 329 endometrial cancer cases and 339 matched controls. AntiMullerian hormone concentrations in blood were quantified using an enzyme-linked immunosorbent assay. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) across tertiles and for a doubling of AMH concentrations (ORlog2). Subgroup analyses were performed by ages at blood donation and diagnosis, oral contraceptive use, and tumour characteristics. Results: Anti-Mullerian hormone was not associated with the risk of endometrial cancer overall (ORlog(2): 1.07 (0.99-1.17)), or with any of the examined subgroups. Conclusions: Although experimental models implicate AMH in endometrial cancer growth inhibition, our findings do not support a role for circulating AMH in the aetiology of endometrial cancer.
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| 6. |
- Ghuan, Sundeep, et al.
(författare)
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Serum inflammatory markers and colorectal cancer risk and survival
- 2017
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Ingår i: British Journal of Cancer. - : NATURE PUBLISHING GROUP. - 0007-0920 .- 1532-1827. ; 116:10, s. 1358-1365
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Tidskriftsartikel (refereegranskat)abstract
- Background: Inflammation has been linked with development of some cancers. We investigated systemic inflammation in relation to colorectal cancer incidence and subsequent survival using common serum inflammatory markersDesign: A cohort of men and women aged 20 years and older in greater Stockholm area with serum C-reactive protein (CRP) and albumin measured between 1986 and 1999 were included (n-325 599). A subset of these had baseline measurements of haptoglobin and leukocytes. Multivariable Cox regression was performed to assess risk of colorectal cancer by levels of inflammatory markers, adjusting for potential confounders. Analyses were stratified by circulating glucose, total cholesterol and triglycerides. Overall and CRC-specific death following diagnosis were assessed as secondary outcomes.Results: A total of 4764 individuals were diagnosed with colorectal cancer. A positive association between haptoglobin and colorectal cancer incidence was found (hazard ratio (HR): 1.17; 95% CI: 1.06-1.28). A positive association was also observed with leukocytes (HR: 1.21; 95% CI: 1.03-1.42). No evidence of association was noted between CRP and colorectal cancer risk. Higher risks of all-cause death were seen with haptoglobin and leukocytes levels. Higher haptoglobin levels were linked with an increased risk of colorectal cancer death (HR: 1.19; 95% CI: 1.01-1.41).Conclusions: Prediagnostic systemic inflammation may impact colorectal cancer incidence and survival; therefore, prompting investigations linking inflammatory pathways preceding colorectal cancer with disease severity and progression.
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| 7. |
- Guren, Tormod Kyrre, et al.
(författare)
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Cetuximab in treatment of metastatic colorectal cancer : final survival analyses and extended RAS data from the NORDIC-VII study
- 2017
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Ingår i: British Journal of Cancer. - : NATURE PUBLISHING GROUP. - 0007-0920 .- 1532-1827. ; 116:10, s. 1271-1278
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Tidskriftsartikel (refereegranskat)abstract
- Background: The NORDIC-VII study is a randomised phase III trial of cetuximab plus continuous or intermittent fluorouracil, folinic acid, and oxaliplatin (Nordic FLOX) vs FLOX alone in first-line treatment of metastatic colorectal cancer. The present report presents an updated and final survival analysis with BRAF and extended RAS mutational status, 5 years after the primary analysis.Methods: A total of 566 patients were included in the intention-to-treat (ITT) population of the NORDIC-VII study. Updated survival status was obtained from 176 patients who were alive in the primary survival analyses. Samples from 223 tumours previously found to be KRAS (exon 2) and BRAF (V600E) wild-type, were re-analysed for KRAS (exons 3 and 4) and NRAS (exons 2-4) mutations.Results: Including the extended RAS analyses, RAS and BRAF mutational status was available from 457 patients (81% of the ITT population). RAS was mutated in 46% and BRAF in 12% of the tumours. RAS and BRAF, if mutated, were negative prognostic factors. The updated analyses confirmed the finding of the primary report that cetuximab did not provide any additional benefit when added to FLOX in patients with RAS/BRAF wild-type tumours, neither on progression-free nor overall survival. However, the outcomes in a subset of patients, which, after the first eight treatment cycles, received cetuximab alone, suggested a beneficial effect of cetuximab monotherapy.Conclusions: Adding cetuximab to Nordic FLOX did not provide any clinical benefit, but the data suggested an effect of cetuximab monotherapy in patients with RAS/BRAF wild-type tumours in the NORDIC-VII cohort. The data were compatible with a negative interaction between cetuximab and the Nordic FLOX chemotherapy backbone.
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| 8. |
- Lindemann, Kristina, et al.
(författare)
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Chemotherapy vs tamoxifen in platinum-resistant ovarian cancer: a phase III, randomised, multicentre trial (Ovaresist)
- 2017
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Ingår i: British Journal of Cancer. - : NATURE PUBLISHING GROUP. - 0007-0920 .- 1532-1827. ; 116:4, s. 455-463
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 9. |
- Martikainen, Miika, et al.
(författare)
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Oncolytic alphavirus SFV-VA7 efficiently eradicates subcutaneous and orthotopic human prostate tumours in mice
- 2017
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Ingår i: British Journal of Cancer. - : NATURE PUBLISHING GROUP. - 0007-0920 .- 1532-1827. ; 117:1, s. 51-55
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Tidskriftsartikel (refereegranskat)abstract
- 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.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.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.Conclusions: Our results indicate that SFV-VA7 is a novel, promising therapeutic virus against prostate cancer warranting further testing in early clinical trials.
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| 10. |
- Pulkka, Olli Pekka, et al.
(författare)
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SLUG transcription factor : A pro-survival and prognostic factor in gastrointestinal stromal tumour
- 2017
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 116:9, s. 1195-1202
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Tidskriftsartikel (refereegranskat)abstract
- Background:The SLUG transcription factor has been linked with the KIT signalling pathway that is important for gastrointestinal stromal tumour (GIST) tumourigenesis. Its clinical significance in GIST is unknown.Methods:Influence of SLUG expression on cell proliferation and viability were investigated in GIST48 and GIST882 cell lines. The association between tumour SLUG expression in immunohistochemistry and recurrence-free survival (RFS) was studied in two clinical GIST series, one with 187 patients treated with surgery alone, and another one with 313 patients treated with surgery and adjuvant imatinib.Results:SLUG downregulation inhibited cell proliferation, induced cell death in both cell lines, and sensitised GIST882 cells to lower imatinib concentrations. SLUG was expressed in 125 (25.0%) of the 500 clinical GISTs evaluated, and expression was associated with several factors linked with unfavourable prognosis. SLUG expression was associated with unfavourable RFS both when patients were treated with surgery alone (HR=3.40, 95% CI=1.67-6.89, P=0.001) and when treated with surgery plus adjuvant imatinib (HR=1.83, 95% CI=1.29-2.60, P=0.001).Conclusions:GIST patients with high tumour SLUG expression have unfavourable RFS. SLUG may mediate pro-survival signalling in GISTs.
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