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- Berger, Karoline, et al.
(författare)
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Reduction of Progranulin-Induced Breast Cancer Stem Cell Propagation by Sortilin-Targeting Cyclotriazadisulfonamide (CADA) Compounds
- 2021
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 64:17, s. 12865-12876
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Tidskriftsartikel (refereegranskat)abstract
- Cyclotriazadisulfonamide (CADA) compounds selectively down- modulate two human proteins of potential therapeutic interest, cluster of differentiation 4 (CD4) and sortilin. Progranulin is secreted from some breast cancer cells, causing dedifferentiation of receiving cancer cells and cancer stem cell proliferation. Inhibition of progranulin binding to sortilin, its main receptor, can block progranulin-induced metastatic breast cancer using a triple-negative in vivo xenograft model. In the current study, seven CADA compounds (CADA, VGD020, VGD071, TL020, TL023, LAL014, and DJ010) were examined for reduction of cellular sortilin expression and progranulin-induced breast cancer stem cell propagation. In addition, inhibition of progranulin-induced mammosphere formation was examined and found to be most significant for TL020, TL023, VGD071, and LAL014. Full experimental details are given for the synthesis and characterization of the four new compounds (TL020, TL023, VGD071, and DJ010). Comparison of solubilities, potencies, and cytotoxicities identified VGD071 as a promising candidate for future studies using mouse breast cancer models.
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- Kyro, C., et al.
(författare)
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ALKYLRESORCINOLS (BIOMARKERS OF WHOLE-GRAIN INTAKE) AND RISK OF COLORECTAL CANCER IN THE EUROPEAN PROSPECTIVE INVESTIGATION INTO CANCER AND NUTRITION
- 2013
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Ingår i: Annals of Nutrition and Metabolism. - : S. Karger. - 0250-6807 .- 1421-9697. ; 63:Supplement 1, s. 1207-1208
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background and objectives: Few studies have investigatedthe association between whole-grain intake and colorectal cancer.Whole-grain products are one of the dietary items proneto measurement errors, making the use of objective measures,such as biomarkers, highly relevant. The objective of the studywas to investigate the association between biomarkers ofwhole-grain intake, alkylresorcinols, and colorectal cancer ina nested case-control study within the European ProspectiveInvestigation into Cancer and Nutrition (EPIC). Methods: We included 1372 first incident colorectal cancercases and 1372 individually matched controls and calculatedthe incidence rate ratios (IRR) for overall and sub-sites of colorectalcancer using conditional logistic regression adjusted forpotential confounders.Results: Plasma total alkylresorcinol concentrations werenot associated with risk of overall colorectal cancer, proximalcolon cancer or rectal cancer. However, high plasma total alkylresorcinolconcentrations were statistically significantly associatedwith lower incidence of cancer located in the distal (leftor descending) part of the colon. Adjusted IRR of distal coloncancer for highest versus lowest quartile of plasma alkylresorcinolwas 0.48 (95% confidence interval = 0.28 to 0.83). Furthermore,we observed an inverse association with colon cancerfor the Scandinavian part of the participants. Alkylresorcinolsmay be more appropriate as biomarkers in Middle Europe andScandinavia i.e. in areas where whole grains are regularly consumed.Conclusions: Whole-grain intake, assessed by alkylresorcinols,was associated with a lower incidence of distal coloncancer. Alkylresorcinols seem useful as objective biomarkersof whole-grain intake in populations where whole-grains are astaple part of the diet. Acknowledgements: This work was supportedby World Cancer Research Fund International (WCRF)and WCRF Netherlands (WCRF NL) (2011/436), and NordForsk(Centre of Excellence programme HELGA (070015)).
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- Munch Roager, Henrik, et al.
(författare)
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Whole grain-rich diet reduces body weight and systemic low-grade inflammation without inducing major changes of the gut microbiome: A randomised cross-over trial
- 2019
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 68:1, s. 83-93
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Tidskriftsartikel (refereegranskat)abstract
- Objective T o investigate whether a whole grain diet alters the gut microbiome and insulin sensitivity, as well as biomarkers of metabolic health and gut functionality. Design 60 Danish adults at risk of developing metabolic syndrome were included in a randomised cross-over trial with two 8-week dietary intervention periods comprising whole grain diet and refined grain diet, separated by a washout period of =6 weeks. The response to the interventions on the gut microbiome composition and insulin sensitivity as well on measures of glucose and lipid metabolism, gut functionality, inflammatory markers, anthropometry and urine metabolomics were assessed. Results 50 participants completed both periods with a whole grain intake of 179±50 g/day and 13±10 g/day in the whole grain and refined grain period, respectively. Compliance was confirmed by a difference in plasma alkylresorcinols (p<0.0001). Compared with refined grain, whole grain did not significantly alter glucose homeostasis and did not induce major changes in the faecal microbiome. Also, breath hydrogen levels, plasma short-chain fatty acids, intestinal integrity and intestinal transit time were not affected. The whole grain diet did, however, compared with the refined grain diet, decrease body weight (p<0.0001), serum inflammatory markers, interleukin (IL)-6 (p=0.009) and C-reactive protein (p=0.003). The reduction in body weight was consistent with a reduction in energy intake, and IL-6 reduction was associated with the amount of whole grain consumed, in particular with intake of rye. Conclusion C ompared with refined grain diet, whole grain diet did not alter insulin sensitivity and gut microbiome but reduced body weight and systemic lowgrade inflammation.
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- Kvaerner, A. S., et al.
(författare)
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The CRCbiome study: a large prospective cohort study examining the role of lifestyle and the gut microbiome in colorectal cancer screening participants
- 2021
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Ingår i: Bmc Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Colorectal cancer (CRC) screening reduces CRC incidence and mortality. However, current screening methods are either hampered by invasiveness or suboptimal performance, limiting their effectiveness as primary screening methods. To aid in the development of a non-invasive screening test with improved sensitivity and specificity, we have initiated a prospective biomarker study (CRCbiome), nested within a large randomized CRC screening trial in Norway. We aim to develop a microbiome-based classification algorithm to identify advanced colorectal lesions in screening participants testing positive for an immunochemical fecal occult blood test (FIT). We will also examine interactions with host factors, diet, lifestyle and prescription drugs. The prospective nature of the study also enables the analysis of changes in the gut microbiome following the removal of precancerous lesions. Methods: The CRCbiome study recruits participants enrolled in the Bowel Cancer Screening in Norway (BCSN) study, a randomized trial initiated in 2012 comparing once-only sigmoidoscopy to repeated biennial FIT, where women and men aged 50-74 years at study entry are invited to participate. Since 2017, participants randomized to FIT screening with a positive test result have been invited to join the CRCbiome study. Self-reported diet, lifestyle and demographic data are collected prior to colonoscopy after the positive FIT-test (baseline). Screening data, including colonoscopy findings are obtained from the BCSN database. Fecal samples for gut microbiome analyses are collected both before and 2 and 12 months after colonoscopy. Samples are analyzed using metagenome sequencing, with taxonomy profiles, and gene and pathway content as primary measures. CRCbiome data will also be linked to national registries to obtain information on prescription histories and cancer relevant outcomes occurring during the 10 year follow-up period. Discussion: The CRCbiome study will increase our understanding of how the gut microbiome, in combination with lifestyle and environmental factors, influences the early stages of colorectal carcinogenesis. This knowledge will be crucial to develop microbiome-based screening tools for CRC. By evaluating biomarker performance in a screening setting, using samples from the target population, the generalizability of the findings to future screening cohorts is likely to be high.
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- Laslett, Anne-Marie, et al.
(författare)
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A Multi-Country Study of Harms to Children Because of Others' Drinking
- 2017
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Ingår i: Journal of Studies on Alcohol and Drugs. - : Alcohol Research Documentation, Inc.. - 1937-1888 .- 1938-4114. ; 78:2, s. 195-202
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This study aims to ascertain and compare the prevalence and correlates of alcohol-related harms to children cross nationally. Method: National and regional sample surveys of randomly selected households included 7,848 carers (4,223 women) from eight countries (Australia, Chile, Ireland, Lao People's Democratic Republic [PDR], Nigeria, Sri Lanka, Thailand, and Vietnam). Country response rates ranged from 35% to 99%. Face-to-face or telephone surveys asking about harm from others' drinking to children ages 0-17 years were conducted, including four specific harms: that because of others' drinking in the past year children had been (a) physically hurt, (b) verbally abused, (c) exposed to domestic violence, or (d) left unsupervised. Results: The prevalence of alcohol-related harms to children varied from a low of 4% in Lao PDR to 14% in Vietnam. Alcohol-related harms to children were reported by a substantial minority of families in most countries, with only Lao PDR and Nigeria reporting significantly lower levels of harm. Alcohol-related harms to children were dispersed sociodemographically and were concentrated in families with heavy drinkers. Conclusions: Family-level drinking patterns were consistently identified as correlates of harm to children because of others' drinking, whereas sociodemographic factors showed few obvious correlations.
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- Monfort-Pires, M., et al.
(författare)
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Serum short-chain fatty acids are associated with brown adipose tissue metabolism in humans
- 2023
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Ingår i: Diabetologia. - 1432-0428 .- 0012-186X. ; 66:SUPPL 1, s. S297-S298
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Short-chain fatty acids (SCFAs) result from the fermentation of dietary fibre in the colon and are shown to play an important role in energy metabolism. The relationship between circulating SCFA and brown adipose tissue (BAT) in humans remains to be clarified. We investigated the associations between circulating SCFA and BAT function in humans.
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| 10. |
- Skeie, G., et al.
(författare)
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Intake of whole grains and incidence of gastric and oesophageal cancer in the HELGA cohort
- 2013
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Ingår i: Annals of Nutrition and Metabolism. - : S. Karger. - 0250-6807 .- 1421-9697. ; 63:Supplement 1, s. 198-199
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background and objectives: Whole grains are a good sourceof dietary fibre, but beneficial effects might also stem fromother components of the grain. Very few studies exist on intakeof whole grains and incidence of stomach and oesophagealcancer, but studies on dietary fibre and these cancers suggesta protective effect. The objective of this work was to study theassociation between intake of whole grains and incidence ofoesophageal and gastric cancer. Methods: The Helga cohort has 120 000 participants fromthe Norwegian Women and Cancer study, The Northern Sweden Health and Disease study and the Danish Diet, Cancerand Health study, recruited in 1992-1999. After exclusions, 112cases of oesophageal cancer, 185 cases of gastric cancer and 113700 other cohort members were included in the analyses. Theyprovided dietary information in semi-quantitative FFQs at baseline,and also information about other risk factors. Cancer information was obtained by linkage to the respective cancerregistries. The association between whole grain intake and cancerwas analysed with Cox proportional hazards models. Results: The median whole-grain intake was 47.4 g/day(5th-95th percentile: 13.3-101.1) in the non-cases, 37.5 g/day(10.8-87.2) in oesophageal cancer cases, and 45.1 g/day (8.1-99.1) in gastric cancer cases. A decreased risk of oesophagealcancer was observed, HR=0.83 (CI 0.69-0.99) p=0.04 per 20g of whole grains. The HR for highest compared with lowesttertile of intake was 0.56 (0.32-0.97) p=0.03. The analyses wereadjusted for country, smoking status, age at baseline, sex, processedmeat, alcohol and vitamin C. No association was foundfor whole grains and gastric cancer.Conclusion: In this study, higher intake of whole grains wasassociated with lower risk of oesophageal cancer. Acknowledgements: This work was supported by NordForsk– Centre of excellence programme HELGA (070015).
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