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| 3. |
- Egeler, M.D., et al.
(författare)
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Understanding quality of life issues in patients with advanced melanoma : Phase 1 and 2 in the development of the EORTC advanced melanoma module
- 2024
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Ingår i: European Journal of Cancer. - : Elsevier. - 0959-8049 .- 1879-0852. ; 207
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Tidskriftsartikel (refereegranskat)abstract
- Aims: We aimed to develop a European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) module tailored for patients with advanced (resectable or unresectable stage III/IV) melanoma receiving immune checkpoint inhibitors or targeted therapy.Methods: Following the EORTC QoL Group module development guidelines, we conducted phases 1 and 2 of the development process. In phase 1, we generated a list of health-related (HR)QoL issues through a systematic literature review and semi-structured interviews with healthcare professionals (HCPs) and patients with advanced melanoma. In phase 2, these issues were converted into questionnaire items to create the preliminary module.Results: Phase 1: we retrieved 8006 articles for the literature review, of which 35 were deemed relevant, resulting in 84 HRQoL issues being extracted to create the initial issue list. Semi-structured interviews with 18 HCPs and 28 patients with advanced melanoma resulted in 28 issues being added to the initial issue list. Following EORTC module development criteria, 26 issues were removed, and two issues were added after review by patient advocates.Phase 2: To ensure uniformity and avoid duplication, 16 issues were consolidated into eight items. Additionally, an independent expert contributed one new item, resulting in a preliminary module comprising 80 HRQoL items.Conclusion: We identified a range of HRQoL issues (dry skin, xerostomia, and arthralgia) relevant to patients with stage III/IV melanoma. Future module development phases will refine the questionnaire. Once completed, this module will enable standardized assessment of HRQoL in patients with (locally) advanced melanoma.
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- Van Hemelrijck, Mieke, et al.
(författare)
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Reasons for Discontinuing Active Surveillance : Assessment of 21 Centres in 12 Countries in the Movember GAP3 Consortium
- 2019
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838. ; 75:3, s. 523-531
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Tidskriftsartikel (refereegranskat)abstract
- Background: Careful assessment of the reasons for discontinuation of active surveillance (AS) is required for men with prostate cancer (PCa). Objective: Using Movember's Global Action Plan Prostate Cancer Active Surveillance initiative (GAP3) database, we report on reasons for AS discontinuation. Design, setting, and participants: We compared data from 10 296 men on AS from 21 centres across 12 countries. Outcome measurements and statistical analysis: Cumulative incidence methods were used to estimate the cumulative incidence rates of AS discontinuation. Results and limitations: During 5-yr follow-up, 27.5% (95% confidence interval [CI]: 26.4–28.6%) men showed signs of disease progression, 12.8% (95% CI: 12.0–13.6%) converted to active treatment without evidence of progression, 1.7% (95% CI: 1.5–2.0%) continued to watchful waiting, and 1.7% (95% CI: 1.4–2.1%) died from other causes. Of the 7049 men who remained on AS, 2339 had follow-up for >5 yr, 4561 had follow-up for <5 yr, and 149 were lost to follow-up. Cumulative incidence of progression was 27.5% (95% CI: 26.4–28.6%) at 5 yr and 38.2% (95% CI: 36.7–39.9%) at 10 yr. A limitation is that not all centres were included due to limited information on the reason for discontinuation and limited follow-up. Conclusions: Our descriptive analyses of current AS practices worldwide showed that 43.6% of men drop out of AS during 5-yr follow-up, mainly due to signs of disease progression. Improvements in selection tools for AS are thus needed to correctly allocate men with PCa to AS, which will also reduce discontinuation due to conversion to active treatment without evidence of disease progression. Patient summary: Our assessment of a worldwide database of men with prostate cancer (PCa) on active surveillance (AS) shows that 43.6% drop out of AS within 5 yr, mainly due to signs of disease progression. Better tools are needed to select and monitor men with PCa as part of AS.
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- Rammant, E., et al.
(författare)
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The current use of the EORTC QLQ-NMIBC24 and QLQ-BLM30 questionnaires for the assessment of health-related quality of life in bladder cancer patients : a systematic review
- 2023
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Ingår i: Quality of Life Research. - : Springer Science and Business Media LLC. - 0962-9343 .- 1573-2649. ; 32:8, s. 2127-2135
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Forskningsöversikt (refereegranskat)abstract
- Purpose: Investigating the use of the EORTC bladder cancer (BC) modules by evaluating: (a) study contexts/designs; (b) languages/countries in which the modules were administered; (c) their acceptance by patients/investigators; and (d) their psychometric properties. Methods: A systematic review was performed with studies from 1998 until 20/10/2021 in five databases. Articles/conference abstracts using the EORTC-QLQBLM30 (muscle invasive BC) and the EORTC-QLQNMIBC24 (previously referred to as QLQ-BLS24; non-muscle invasive BC) were included. Two authors independently screened titles/abstracts/full-texts and performed data extraction. Results: A total of 76 eligible studies were identified. Most studies included the BLM30 (n = 53), were in a urological surgery context (n = 41) and were cross-sectional (n = 35) or prospective (n = 30) in design. The BC modules were administered in 14 languages across 19 countries. Missing data were low-moderate for all non-sex related questions (< 1% to 15%). Sex-related questions had higher rates of missing data (ranging from 6.9% to 84%). Most investigators did not use all scales of the questionnaires. One validation study for the original BLS24 led to the development of the NMIBC24, which adopted a new scale structure for which good structural validity was confirmed (n = 3). Good reliability and validity was shown for the NMIBC24 module, except for malaise and bloating/flatulence scales. Psychometric evidence for BLM30 is lacking. Conclusion: These results provide insight into how the EORTC BC quality of life modules could be further improved. Current work is ongoing to update the modules and to determine if the two modules can be combined into a single questionnaire that works well in both the NMIBC and MIBC settings.
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- Wulaningsih, W., et al.
(författare)
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A competing risks analysis of the association between prediagnostic serum glucose and lipids and breast cancer survival
- 2016
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Ingår i: Cancer Research. - Kings Coll London, Div Canc Studies, Canc Epidemiol Grp, London WC2R 2LS, England. Kings Coll London, Inst Math & Mol Biomed, London WC2R 2LS, England. Uppsala Univ, Uppsala, Sweden. Reg Canc Ctr, Uppsala, Sweden. Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden. Karolinska Inst, S-10401 Stockholm, Sweden. AstraZeneca R&D, Mlndal, Switzerland. CALAB Res, Madrid, Spain.. - 0008-5472 .- 1538-7445. ; 76
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 13. |
- Zylstra, J, et al.
(författare)
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Exercise prehabilitation during neoadjuvant chemotherapy may enhance tumour regression in oesophageal cancer: results from a prospective non-randomised trial
- 2022
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Ingår i: British journal of sports medicine. - : BMJ. - 1473-0480 .- 0306-3674. ; 56:7, s. 402-
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Tidskriftsartikel (refereegranskat)abstract
- There is increasing evidence for the use of exercise in cancer patients and data supporting enhanced tumour volume reduction following chemotherapy in animal models. To date, there is no reported histopathological evidence of a similar oncological benefit in oesophageal cancer.MethodsA prospective non-randomised trial compared a structured prehabilitation exercise intervention during neoadjuvant chemotherapy and surgery versus conventional best-practice for oesophageal cancer patients. Biochemical and body composition analyses were performed at multiple time points. Outcome measures included radiological and pathological markers of disease regression. Logistic regression calculated ORs with 95% CI for the likelihood of pathological response adjusting for chemotherapy regimen and chemotherapy delivery.ResultsComparison of the Intervention (n=21) and Control (n=19) groups indicated the Intervention group had higher rates of tumour regression (Mandard TRG 1–3 Intervention n=15/20 (75%) vs Control n=7/19 (36.8%) p=0.025) including adjusted analyses (OR 6.57; 95% CI 1.52 to 28.30). Combined tumour and node downstaging (Intervention n=9 (42.9%) vs Control n=3 (15.8%) p=0.089) and Fat Free Mass index were also improved (Intervention 17.8 vs 18.7 kg/m2; Control 16.3 vs 14.7 kg/m2, p=0.026). Differences in markers of immunity (CD-3 and CD-8) and inflammation (IL-6, VEGF, INF-y, TNFa, MCP-1 and EGF) were observed.ConclusionThe results suggest improved tumour regression and downstaging in the exercise intervention group and should prompt larger studies on this topic.Trial registration numberNCT03626610.
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| 17. |
- Rowley, M., et al.
(författare)
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A latent class model for competing risks
- 2017
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Ingår i: Statistics in Medicine. - : Wiley. - 0277-6715 .- 1097-0258. ; 36:13, s. 2100-2119
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Tidskriftsartikel (refereegranskat)abstract
- Survival data analysis becomes complex when the proportional hazards assumption is violated at population level or when crude hazard rates are no longer estimators of marginal ones. We develop a Bayesian survival analysis method to deal with these situations, on the basis of assuming that the complexities are induced by latent cohort or disease heterogeneity that is not captured by covariates and that proportional hazards hold at the level of individuals. This leads to a description from which risk-specific marginal hazard rates and survival functions are fully accessible, 'decontaminated' of the effects of informative censoring, and which includes Cox, random effects and latent classmodels as special cases. Simulated data confirm that our approach can map a cohort's substructure and remove heterogeneity-induced informative censoring effects. Application to data from the Uppsala Longitudinal Study of Adult Men cohort leads to plausible alternative explanations for previous counter-intuitive inferences on prostate cancer. The importance of managing cardiovascular disease as a comorbidity in women diagnosed with breast cancer is suggested on application to data from the Swedish Apolipoprotein Mortality Risk Study.
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| 18. |
- van Leeuwen, Marieke, et al.
(författare)
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Phase III study of the European Organisation for Research and Treatment of Cancer Quality of Life cancer survivorship core questionnaire
- 2023
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Ingår i: Journal of Cancer Survivorship. - : Springer Science and Business Media LLC. - 1932-2259 .- 1932-2267. ; 17:4, s. 1111-1130
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The purpose of this study is to develop a European Organisation for Research and Treatment of Cancer Quality of Life Group (EORTC QLG) questionnaire that captures the full range of physical, mental, and social health-related quality of life (HRQOL) issues relevant to disease-free cancer survivors. In this phase III study, we pretested the provisional core questionnaire (QLQ-SURV111) and aimed to identify essential and optional scales. Methods: We pretested the QLQ-SURV111 in 492 cancer survivors from 17 countries with one of 11 cancer diagnoses. We applied the EORTC QLG decision rules and employed factor analysis and item response theory (IRT) analysis to assess and, where necessary, modify the hypothesized questionnaire scales. We calculated correlations between the survivorship scales and the QLQ-C30 summary score and carried out a Delphi survey among healthcare professionals, patient representatives, and cancer researchers to distinguish between essential and optional scales. Results: Fifty-four percent of the sample was male, mean age was 60 years, and, on average, time since completion of treatment was 3.8 years. Eleven items were excluded, resulting in the QLQ-SURV100, with 12 functional and 9 symptom scales, a symptom checklist, 4 single items, and 10 conditional items. The essential survivorship scales consist of 73 items. Conclusions: The QLQ-SURV100 has been developed to assess comprehensively the HRQOL of disease-free cancer survivors. It includes essential and optional scales and will be validated further in an international phase IV study. Implications for Cancer Survivors: The availability of this questionnaire will facilitate a standardized and robust assessment of the HRQOL of disease-free cancer survivors.
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| 19. |
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| 20. |
- Arthur, R., et al.
(författare)
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Serum inflammatory markers in relation to prostate cancer severity and death in the Swedish AMORIS study
- 2018
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Ingår i: International Journal of Cancer. - : WILEY. - 0020-7136 .- 1097-0215. ; 142:11, s. 2254-2262
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Tidskriftsartikel (refereegranskat)abstract
- Inflammation is a well-documented driver of cancer development and progression. However, little is known about its role in prostate carcinogenesis. Thus, we examined the association of C-reactive protein (CRP), haptoglobin, albumin and white blood cells (WBC) with prostate cancer (PCa) severity (defined by PCa risk category and clinicopathological characteristics) and progression (defined by PCa death). We selected 8,471 Swedish men with newly diagnosed PCa who had exposure measurements taken approximately 14 years prior to diagnosis. We calculated odds ratio (OR) and 95% confidence interval (CI) for the associations between the inflammatory markers and PCa severity using logistic regression, while Cox proportional hazard regression was used for the associations with overall and PCa death. Serum CRP levels were associated with increased odds of high risk and metastatic PCa, and high PSA levels (20 mu g/L) (OR: 1.29; 95% CI: 1.06-1.56, 1.32; 1.05-1.65 and 1.51; 1.26-1.81, respectively). Similarly, higher haptoglobin levels were associated with increased odds of metastatic PCa, high PSA level and possibly high grade PCa (1.38; 1.10-1.74, 1.50; 1.17-1.93 and 1.25; 1.00-1.56, respectively). Albumin was positively associated with Gleason 4+3 tumour (1.38; 1.02-1.86) and overall death (HRunit increase in log: 1.60; 95% CI: 1.11-2.30), but inversely associated with high risk PCa and high PSA levels (20 mu g/L) (0.71; 0.56-0.89 and 0.72; 0.5 9-0.90). WBC was associated with increased odds of T3-T4 PCa. Except for albumin, none of these markers were associated with PCa death or overall death. Systemic inflammation as early as 14 years prior to diagnosis may influence prostate cancer severity. What's new? High levels of C-reactive protein can presage a particularly malignant prostate cancer, new results show. Cancers certainly arise in the wake of chronic inflammation, but it's not known exactly how markers of inflammation initiate prostate cancer. Here, the authors show that systemic inflammation can worsen the severity of the cancer, even if it occurred long before the cancer's onset. High levels of CRP and haptoglobin, they found, were associated with prostate cancer with high PSA and metastasis. The question remains whether inflammation pushes cancer cells into a more malignant mode, or selects for the more dangerous cells early on.
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| 33. |
- Van Hemelrijck, M, et al.
(författare)
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Lipid profiles and the risk of kidney cancer in the Swedish AMORIS study
- 2011
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Ingår i: JOURNAL OF CLINICAL ONCOLOGY. - : American Society of Clinical Oncology (ASCO). - 0732-183X .- 1527-7755. ; 29:7
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- 342 Background: Since multiple epidemiologic studies showed a link between obesity and kidney cancer (KCa), the lipid metabolism is thought to play a role in development of KCa. With the exception of cholesterol and total fat intake, the association between changes in lipid biomarkers and KCa has not often been researched. We assessed the link between lipid profiles and KCa risk in a large prospective cohort study. Methods: A cohort based on 85,261 persons (> 20 years old) with baseline measurements of glucose, triglycerides (TG), total cholesterol, HDL, LDL, apolipoprotein A-I and apoB was selected from the Swedish Apolipoprotein Mortality Risk (AMORIS) study. Multivariate Cox proportional hazards models were used to analyze associations between quartiles and dichotomized values of these lipid components and KCa risk. All models were adjusted for age, gender, socioeconomic status, fasting status, history of kidney disease prior to baseline (ICD9: 580-93), and glucose, cholesterol, and TG levels (depending on the covariate of interest). Results: During a mean follow-up of 12 years, 161 persons developed KCa (58% men). The mean age at baseline was 46 years. TG were the only lipid component for which a statistically significant association was found with risk of KCa (Hazard Ratio (HR): 1.05 (95%CI: 0.59-1.87), 1.77 (1.05-2.98), and 1.77 (1.04-3.02) for the second, third, and fourth quartile, compared to the first, with p-value for trend: 0.008). The lipid ratio of TG and HDL also showed a statistically significant positive association with risk of KCa (HR: 1.21 (0.71-2.08), 1.56 (0.94-2.58), and 1.92 (1.17-3.17) for the second, third, and fourth quartile, compared to the first, with p-value for trend: 0.004). No other associations were found between lipid components and KCa risk. Conclusions: This detailed analysis of lipid components and risk of KCa found a relation between levels of TG and KCa risk. In contrast to previous studies, we did not find an association between cholesterol levels and KCa risk. Lipid profiles based on the markers used in this study do not seem to reflect the etiological pathway that has previously been shown between obesity and KCa. Further mechanistic studies are required to assess the link between lipid deregulation and KCa. No significant financial relationships to disclose.
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| 35. |
- Van Hemelrijck, M, et al.
(författare)
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Serum calcium and incident and fatal prostate cancer in the Swedish AMORIS study
- 2012
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Ingår i: JOURNAL OF CLINICAL ONCOLOGY. - : American Society of Clinical Oncology (ASCO). - 0732-183X .- 1527-7755. ; 30:5
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- 36 Background: Many observational studies have shown a positive association between intake of dairy products and prostate cancer (PCa) risk. From a biological point of view it is of interest to study this association as bone was recently shown to be a positive regulator of male fertility which suggests that regulation of bone remodeling and reproduction are linked. Since androgens promote cell proliferation and inhibit prostate cell death, it is possible that calcium (Ca) is linked to PCa risk via its link with the reproductive system. We studied the association between serum Ca and PCa while also accounting for levels of albumin, a protein to which Ca is bound. Methods: A cohort based on 192,183 men with baseline information on Ca (mmol/L) and albumin (g/L) was selected from the Swedish Apolipoprotein MOrtality RISk (AMORIS) study. Age-stratified multivariable Cox proportional hazard models were used to analyze associations between Ca and incident and fatal PCa risk. All models were adjusted for fasting status, glucose levels, socio-economic status, season at time of Ca measurement, Charlson comorbidity index, and history of fractures. Results: A 6,202 men were diagnosed with PCa and 672 died of PCa during mean follow-up of 12 years. A weak negative association was found between PCa risk and Ca (HR per SD: 0.97 (95%CI: 0.95-1.00)). A similar association was also found between albumin-corrected Ca and PCa risk (HR: 0.96 (0.89-1.03), 0.94 (0.87-1.01), and 0.92 (0.86-0.99) for the 2nd, 3rd, and 4th quartile compared to the 1st; P for trend: 0.02). No association was found with fatal PCa, nor was there effect-modification by overweight. A strong positive association between Ca and death was observed when censoring for PCa (HR per SD: 1.13 (95%CI: 1.12-1.15)). Conclusions: Serum levels of Ca were weakly negatively associated with PCa risk in our study when adjusted for age and history of comorbidities and fractures. A negative association between Ca and PCa risk is likely explained by the strong relation between Ca and non-PCa death. These competing risks need to be handled in order to define whether Ca is causally involved in PCa aetiology or whether it only acts a marker of other metabolic events in the causal pathway.
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| 36. |
- Walldius, G, et al.
(författare)
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Cohort Profile: The AMORIS cohort
- 2017
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Ingår i: International journal of epidemiology. - : Oxford University Press (OUP). - 1464-3685 .- 0300-5771. ; 46:4, s. 1103-
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Tidskriftsartikel (refereegranskat)
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| 37. |
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| 42. |
- Beyer, Katharina, et al.
(författare)
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A Systematic Review of Heterogeneity in Outcome Definition and Reporting in Localised Renal Cancer
- 2023
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Ingår i: European Urology Open Science. - : Elsevier BV. - 2666-1691 .- 2666-1683. ; 48, s. 1-11
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Forskningsöversikt (refereegranskat)abstract
- Context: Outcomes in renal cell carcinoma (RCC) are reported inconsistently, with variability in definitions and measurement. Hence, it is difficult to compare intervention effectiveness and synthesise outcomes for systematic reviews and to create clinical practice guidelines. This uncertainty in the evidence makes it difficult to guide patient-clinician decision-making. One solution is a core outcome set (COS): an agreed minimum set of outcomes. Objective: To describe outcome reporting, definitions, and measurement heterogeneity as the first stage in co-creating a COS for localised renal cancer. Evidence acquisition: We systematically reviewed outcome reporting heterogeneity in effectiveness trials and observational studies in localised RCC. In total, 2822 studies (randomised controlled trials, cohort studies, case-control studies, systematic reviews) up to June 2020 meeting our inclusion criteria were identified. Abstracts and full texts were screened independently by two reviewers; in cases of disagreement, a third reviewer arbitrated. Data extractions were double-checked. Evidence synthesis: We included 149 studies and found that there was inconsistency in which outcomes were reported across studies and variability in the definitions used for outcomes that were conceptually the same. We structured our analysis using the outcome classification taxonomy proposed by Dodd et al. Outcomes linked to adverse events (eg, bleeding, outcomes linked to surgery) and renal injury outcomes (reduced renal function) were reported most commonly. Outcomes related to deaths from any cause and from cancer were reported in 44% and 25% of studies, respectively, although the time point for measurement and the analysis methods were inconsistent. Outcomes linked to life impact (eg, global quality of life) were reported least often. Clinician-reported outcomes are more frequently reported than patient-reported outcomes in the renal cancer literature. Conclusions: This systematic review underscores the heterogeneity of outcome reporting, definitions, and measurement in research on localised renal cancer. It catalogues the variety of outcomes and serves as a first step towards the development of a COS for localised renal cancer. Patient summary: We reviewed studies on localised kidney cancer and found that multiple terms and definitions have been used to describe outcomes. These are not defined consistently, and often not defined at all. Our review is the first phase in developing a core outcome set to allow better comparisons of studies to improve medical care.
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| 43. |
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| 45. |
- Bruinsma, Sophie M, et al.
(författare)
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The Movember Foundation's GAP3 cohort : a profile of the largest global prostate cancer active surveillance database to date
- 2018
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Ingår i: BJU International. - : Wiley. - 1464-4096. ; 121:5, s. 737-744
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The Movember Foundation launched the Global Action Plan Prostate Cancer Active Surveillance (GAP3) initiative to create a global consensus on the selection and monitoring of men with low-risk prostate cancer (PCa) on active surveillance (AS). The aim of this study is to present data on inclusion and follow-up for AS in this unique global AS database.PATIENTS AND METHODS: Between 2014 and 2016, the database was created by combining patient data from 25 established AS cohorts worldwide (USA, Canada, Australasia, UK and Europe). Data on a total of 15 101 patients were included. Descriptive statistics were used to report patients' clinical and demographic characteristics at the time of PCa diagnosis, clinical follow-up, discontinuation of AS and subsequent treatment. Cumulative incidence curves were used to report discontinuation rates over time.RESULTS: At diagnosis, the median (interquartile range [IQR]) patient age was 65 (60-70) years and the median prostate-specific antigen level was 5.4 (4.0-7.3) ng/mL. Most patients had clinical stage T1 disease (71.8%), a biopsy Gleason score of 6 (88.8%) and one tumour-positive biopsy core (60.3%). Patients on AS had a median follow-up time of 2.2 (1.0-5.0) years. After 5, 10 and 15 years of follow-up, respectively, 58%, 39% and 23% of patients were still on AS. The current version of GAP3 has limited data on magnetic resonance imaging (MRI), quality of life and genomic testing.CONCLUSIONS: GAP3 is the largest worldwide collaboration integrating patient data from men with PCa on AS. The results will allow individual patients and clinicians to have greater confidence in the personalized decision to either delay or proceed with active treatment. Longer follow-up and the evaluation of MRI, new genomic markers and patient-related outcomes will result in even more valuable data and eventually in better patient outcomes.
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| 46. |
- Bui, Tuyet T. A., et al.
(författare)
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Botrytis cinerea differentially induces postharvest antioxidant responses in 'Braeburn' and 'Golden Delicious' apple fruit
- 2019
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Ingår i: Journal of the Science of Food and Agriculture. - : John Wiley & Sons. - 0022-5142 .- 1097-0010. ; 99:13, s. 5662-5670
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The fruit of two apple cultivars - 'Braeburn', which is susceptible to inoculation with Botrytis cinerea, and the less susceptible cv. 'Golden Delicious' - were investigated with respect to their response to inoculation with B. cinerea. Successful infection by B. cinerea leads to an oxidative burst and perturbation of plant redox homeostasis. To investigate the interaction between apple fruit and B. cinerea, antioxidant metabolism in fruit samples from sun-exposed and shaded sides of different tissue types was measured over time.RESULTS: The sun-exposed tissue of 'Braeburn' had higher initial levels of total vitamin C in the peel and phenolic compounds in the flesh than 'Golden Delicious', despite its greater susceptibility to gray mold. A substantial antioxidant response was recorded in diseased 'Braeburn' fruit 14 days after inoculation, which involved an elevated superoxide dismutase activity and ascorbate peroxidase activity, a progressive oxidation of total vitamin C, and a decrease in peroxidase activity and phenolic content. Disease development was slower on the sun-exposed sides than on the shaded sides.CONCLUSION: The two cultivars appeared to utilize different strategies to defend themselves against B. cinerea. 'Golden Delicious' almost entirely escaped infection. Preharvest exposure of apple fruit to high light / temperature stress appears to prepare them to better resist subsequent postharvest attack and disease.
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| 47. |
- Crawley, Danielle J., et al.
(författare)
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Serum glucose and risk of cancer : a meta-analysis
- 2014
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Background: Raised serum glucose has been linked to increased risk of many solid cancers. We performed a meta-analysis to quantify and summarise the evidence for this link. Methods: Pubmed and Embase were reviewed, using search terms representing serum glucose and cancer. Inclusion and exclusion criteria focused on epidemiological studies with clear definitions of serum glucose levels, cancer type, as well as well-described statistical methods with sufficient data available. We used 6.1 mmol/L as the cut-off for high glucose, consistent with the WHO definition of metabolic syndrome. Random effects analyses were performed to estimate the pooled relative risk (RR). Results: Nineteen studies were included in the primary analysis, which showed a pooled RR of 1.32 (95% CI: 1.20 - 1.45). Including only those individuals with fasting glucose measurements did not have a large effect on the pooled RR (1.32 (95% CI: 1.11-1.57). A stratified analysis showed a pooled RR of 1.34 (95% CI: 1.02-1.77) for hormonally driven cancer and 1.21 (95% CI: 1.09-1.36) for cancers thought to be driven by Insulin Growth Factor-1. Conclusion: A positive association between serum glucose and risk of cancer was found. The underlying biological mechanisms remain to be elucidated but our subgroup analyses suggest that the insulin- IGF-1 axis does not fully explain the association. These findings are of public health importance as measures to reduce serum glucose via lifestyle and dietary changes could be implemented in the context of cancer mortality.
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| 48. |
- De Piano, Mario, et al.
(författare)
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Lipogenic signalling modulates prostate cancer cell adhesion and migration via modification of Rho GTPases
- 2020
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Ingår i: Oncogene. - : NATURE PUBLISHING GROUP. - 0950-9232 .- 1476-5594. ; 39:18, s. 3666-3679
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Tidskriftsartikel (refereegranskat)abstract
- Fatty acid synthase (FASN) is commonly overexpressed in prostate cancer and associated with tumour progression. FASN is responsible for de novo synthesis of the fatty acid palmitate; the building block for protein palmitoylation. Recent work has suggested that alongside its established role in promoting cell proliferation FASN may also promote invasion. We now find depletion of FASN expression increases prostate cancer cell adhesiveness, impairs HGF-mediated cell migration and reduces 3D invasion. These changes in motility suggest that FASN can mediate actin cytoskeletal remodelling; a process known to be downstream of Rho family GTPases. Here, we demonstrate that modulation of FASN expression specifically impacts on the palmitoylation of the atypical GTPase RhoU. Impaired RhoU activity in FASN depleted cells leads to reduced adhesion turnover downstream of paxillin serine phosphorylation, which is rescued by addition of exogenous palmitate. Moreover, canonical Cdc42 expression is dependent on the palmitoylation status of RhoU. Thus we uncover a novel relationship between FASN, RhoU and Cdc42 that directly influences cell migration potential. These results provide compelling evidence that FASN activity directly promotes cell migration and supports FASN as a potential therapeutic target in metastatic prostate cancer.
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| 49. |
- George, G., et al.
(författare)
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Risk of cardiovascular events in men on abiraterone or enzalutamide combined with GnRH agonists: nation-wide, population-based cohort study in Sweden
- 2021
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 60:4, s. 459-465
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Tidskriftsartikel (refereegranskat)abstract
- Background Men with prostate cancer (PCa) on gonadotropin-releasing hormone agonists (GnRH) have an increased risk of cardiovascular disease (CVD) compared to men with PCa not on GnRH as well as compared with PCa-free men. Whether the addition of androgen receptor targeted (ART) drugs to GnRH further increases CVD risk, remains to be fully elucidated. Material and methods We investigated risk of CVD for men with castration resistant PCa (CRPC) on GnRH plus ART; abiraterone or enzalutamide vs 5,127 and 12,079 respective matched comparator men on GnRH in Prostate Cancer data Base Sweden (PCBaSeTraject) 4.1 between 1 June 2015 and 31 December 2018. PCBaSeTraject links National Prostate Cancer Register of Sweden to other healthcare registries and demographic databases. We conducted multivariable Cox proportional hazard models adjusting for PCa risk category, Charlson comorbidity index (CCI), insulin or statin use, civil status, level of education, history of CVD events and number of CVD drugs, with any incident or fatal CVD as the outcome. Results and conclusion 1,310 men were treated with abiraterone and 3,579 with enzalutamide. In multivariable analysis, CVD risk was increased in men on abiraterone (hazard ratio (HR): 1.19; 95% confidence interval (CI): 1.03-1.38) and in men on enzalutamide (HR: 1.10; 95% CI: 1.01-1.20). Men with a recent CVD (<12 months) including both men on ART as well as comparators had a much higher probability of a new CVD vs men with no prior CVD. CVD risk was mildly increased in men with PCa on GnRH plus abiraterone or enzalutamide vs comparator men on GnRH. Residual confounding and detection bias may at least partly explain this association.
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- Häggström, Christel, et al.
(författare)
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Prospective study of Type 2 diabetes mellitus, anti-diabetic drugs and risk of prostate cancer
- 2017
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Ingår i: Int J Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 140:3, s. 611-617
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Tidskriftsartikel (refereegranskat)abstract
- Type 2 diabetes mellitus (T2DM) has consistently been associated with decreased risk of prostate cancer; however, if this decrease is related to the use of anti-diabetic drugs is unknown. We prospectively studied men in the comparison cohort in the Prostate Cancer data Base Sweden 3.0, with data on T2DM, use of metformin, sulfonylurea and insulin retrieved from national health care registers and demographic databases. Cox proportional hazards regression models were used to compute hazard ratios (HR) and 95% confidence intervals (CI) of prostate cancer, adjusted for confounders. The study consisted of 612,846 men, mean age 72 years (standard deviation; SD = 9 years), out of whom 25,882 men were diagnosed with prostate cancer during follow up, mean time of 5 years (SD = 3 years). Men with more than 1 year's duration of T2DM had a decreased risk of prostate cancer compared to men without T2DM (HR = 0.85, 95% CI = 0.82-0.88) but among men with T2DM, those on metformin had no decrease (HR = 0.96, 95% CI = 0.77-1.19), whereas men on insulin (89%) or sulfonylurea (11%) had a decreased risk (HR = 0.73, 95% CI = 0.55-0.98), compared to men with T2DM not on anti-diabetic drugs. Men with less than 1 year's duration of T2DM had no decrease in prostate cancer risk (HR = 1.11, 95% CI = 0.95-1.31). Our results gave no support to the hypothesis that metformin protects against prostate cancer as recently proposed. However, our data gave some support to an inverse association between T2DM severity and prostate cancer risk.
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