| 1. |
- Björk, Per, et al.
(författare)
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Conjugated polythiophene probes target lysosome-related acidic vacuoles in cultured primary cells
- 2007
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Ingår i: Molecular and Cellular Probes. - : Elsevier BV. - 0890-8508. ; 21:5-6, s. 329-337
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Tidskriftsartikel (refereegranskat)abstract
- Conformation-sensitive optical probes for studying biological processes and structures are of great interest. The present work shows for the first time that conjugated polyelectrolyte (CPE) probes can be used for specific targeting of chromatin, nuclear and cytoplasmatic vesicles, and cytoskeletal components in a complex system of cultured cells. One of the probes could also be used for vital staining of live cells. When bound to different entities, the polythiophene derivative probes emitted light with different colors due to the unique spectral properties of these conformation sensitive probes. The physical pre-requisites for binding could also be exploited for characterization of the target. Unexpectedly, lysosome-related acidic vacuoles were targeted in cultured primary cells by both anionic, cationic, and zwitter-ionic polythiophene derivatives. Pre-treatment with Bafilomycin A1, a specific inhibitor of vacuolar-type H+-ATPase, caused redistribution of the staining. The targeting of lysosome-related acidic vesicles could not be demonstrated in transformed cells (melanoma, neuroblastoma, and prostate cancer cell lines), indicating a difference in the localization, structure, accessibility, or quantity of the target in cultured normal cells as compared with the malignant cell lines. The chemical nature of the conjugated polyelectrolyte complex in the cytoplasmatic vacuoles remains elusive.
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| 2. |
- Bordás, Pál, 1955-, et al.
(författare)
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Interval cancer incidence and episode sensitivity in the Norrbotten mammography screening programme, Sweden
- 2009
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Ingår i: Journal of Medical Screening. - : SAGE Publications. - 0969-1413 .- 1475-5793. ; 16:1, s. 39-45
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To estimate the interval cancer incidence, its determinants and the episode sensitivity in the Norrbotten Mammography Screening Programme (NMSP). SETTING: Since 1989, women aged 40-74 years (n = 55,000) have been invited to biennial screening by the NMSP, Norrbotten county, Sweden. METHODS: Data on 1047 invasive breast cancers from six screening rounds of the NMSP (1989-2002) were collected. We estimated the invasive interval cancer rates, rate ratios and the episode sensitivity using the detection and incidence methods. A linear Poisson-model was used to analyse association between interval cancer incidence and sensitivity. RESULTS: 768 screen-detected and 279 interval cancer cases were identified. The rate ratio of interval cancer decreased with age. The 50-59 year age group showed the highest rate ratio (RR = 0.52, 95% CI 0.41-0.65) and the 70-74 year age group the lowest (RR = 0.23, 95% CI 0.15-0.36). The rate ratios for the early (0-12 months) and late (13-24 months) interval cancers were similar (RR = 0.18, 95% CI 0.15-0.22 and 0.20, 95% CI 0.17-0.24). There was a significantly lower interval cancer incidence in the prevalence round as compared with the incidence rounds. According to the detection method the episode sensitivity increased with age from 57% in the age group 40-49 years to 84% in the age group 70-74 years. The corresponding figures for the incidence method were 50% and 77%, respectively. CONCLUSION: Our study showed an interval cancer incidence of 38% and the episode sensitivity of 62-73%, depending on the method of calculation. Our results are of clinically acceptable level and concert with the reference values of the European guidelines.
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| 3. |
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| 4. |
- Brekke, Hilde Kristin, 1972, et al.
(författare)
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Lifestyle modification improves risk factors in type 2 diabetes relatives.
- 2005
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Ingår i: Diabetes research and clinical practice. - : Elsevier BV. - 0168-8227. ; 68:1, s. 18-28
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To investigate the short-term (16 weeks) effect of lifestyle intervention on insulin sensitivity, anthropometric and metabolic variables in non-diabetic first-degree relatives of type 2 diabetic patients (FDR). METHODS: Seventy-seven (49 male, 28 female) FDR were allocated to one of three groups, diet (D-group; n = 25), diet and exercise (DE-group; n = 30) or control group (C-group; n = 22). Lifestyle counselling was based on current nutrition recommendations, including increased intake of fatty fish and low glycaemic index foods. Group counselling was given on two occasions with follow-up through telephone interviews every 10 days. Assessments included insulin sensitivity index (Si), anthropometry, lipid parameters, circulating leptin and adiponectin levels. RESULTS: The D-group reduced total cholesterol (-0.31 mmol/l, P = 0.024), LDL cholesterol (-0.22 mmol/l, P = 0.021) and apolipoprotein B (-9.5 mg/dl, P = 0.009) levels, whereas the DE-group decreased body weight (-2.1%, P = 0.030) and waist circumference (-3.0 cm, P < 0.001) versus controls. A 13% reduction in fasting insulin was observed in the DE-group, but no significant improvement in Si in D-group or DE-group was observed. A subgroup, adherent to diet and who increased exercise, significantly improved Si and lipid profile. CONCLUSIONS: The improved metabolic risk profile in FDR suggests that lifestyle changes can be effective in individuals at high risk to develop type 2 diabetes and cardiovascular disease.
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| 5. |
- Brekke, Hilde Kristin, 1972, et al.
(författare)
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Long-term (1- and 2-year) effects of lifestyle intervention in type 2 diabetes relatives.
- 2005
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Ingår i: Diabetes research and clinical practice. - : Elsevier BV. - 0168-8227. ; 70:3, s. 225-34
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To study the long-term (1- and 2-year) effect of a lifestyle intervention on non-diabetic first-degree relatives of type 2 diabetic patients, i.e., the 1-year effect of diet versus diet and exercise in relation to a control group and the 2-year sustainability of these treatment effects. METHOD: Seventy-seven healthy first-degree relatives (men and women) between the ages of 25 and 55 were allocated to one of three groups: diet group (D), diet and exercise group (DE) and control group (C). For ethical reasons, after 1 year the control group began the intervention and were followed for another 2 years. Diet and physical activity counselling was based on current nutrition recommendations, including increased intake of fatty fish and low glycaemic index foods. The fatty acid composition of the erythrocyte membrane was studied as an objective measure of dietary change. Assessments included fasting insulin, 2-h insulin, oral glucose tolerance test (OGTT), anthropometry and blood lipid measurements. Groups D and DE received intensive follow-up through unannounced telephone interviews during the first 4 months. RESULTS: Dietary changes were significant at 1 year, and to a large degree sustained at 2 years. Adherence to advice regarding fat quality was confirmed through changes in the fatty acid composition of the erythrocyte membrane. The least active subjects in DE increased their physical activity (PA). At 1 year, group D showed a reduction in the ratio of LDL to HDL cholesterol (p=0.028) while group DE decreased their body weight by 2.7% (p<0.029) and increased HDL (p<0.037) versus controls. At 2 years, cholesterol levels (total, LDL and the ratio LDL/HDL) were reduced within group D and when compared to DE (p=0.022, 0.009, 0.035, respectively). Fasting insulin was reduced within group DE and when compared to group D (p=0.025). CONCLUSIONS: Positive changes in lifestyle, blood lipids and fasting insulin can be achieved and maintained in a non-diabetic population at risk of type 2 diabetes after 2 years.
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| 6. |
- Brendle, Annika, et al.
(författare)
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Polymorphisms in predicted microRNA-binding sites in integrin genes and breast cancer ITGB4 as prognostic marker.
- 2008
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Ingår i: Carcinogenesis. - : Oxford University Press. - 0143-3334 .- 1460-2180. ; 29:7, s. 1394-1399
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Tidskriftsartikel (refereegranskat)abstract
- Integrins control the cell attachment to the extracellular matrix and play an important role in mediating cell proliferation, migration and survival. A number of important cancer-associated integrin genes can be regulated by microRNAs (miRNAs) that bind to their target sites in the 3' untranslated regions. We examined the effect of single-nucleotide polymorphisms (SNPs) in predicted miRNA target sites of six integrin genes (ITGA3, ITGA6, ITGAv, ITGB3, ITGB4 and ITGB5) on breast cancer (BC) risk and clinical outcome. Six SNPs were genotyped in 749 Swedish incident BC cases with detailed clinical data and up to 15 years of follow-up together with 1493 matched controls. We evaluated associations between genotypes and BC risk and clinical tumour characteristics. Survival probabilities were compared between different subgroups. As a novel finding, several SNPs seemed to associate with the hormone receptor status. The strongest association was observed between the A allele of the SNP rs743554 in the ITGB4 gene and oestrogen receptor-negative tumours [odds ratio 2.09, 95% confidence intervals (CIs) 1.19-3.67]. The same SNP was associated with survival. The A allele carriers had a worse survival compared with the wild-type genotype carriers (hazard ratio 2.11, 95% CIs 1.21-3.68). The poor survival was significantly associated with the aggressive tumour characteristics: high grade, lymph node metastasis and high stage. None of the SNPs was significantly associated with BC risk. As the ITGB4 SNP seems to influence tumour aggressiveness and survival, it may have prognostic value in the clinic.
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| 7. |
- Brendle, Annika, et al.
(författare)
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Single nucleotide polymorphisms in chromosomal instability genes and risk and clinical outcome of breast cancer : a Swedish prospective case-control study.
- 2009
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Ingår i: European journal of cancer (Oxford, England : 1990). - : Elsevier BV. - 1879-0852 .- 0959-8049. ; 45:3, s. 435-442
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Tidskriftsartikel (refereegranskat)abstract
- Chromosomal instability (CIN) is a major characteristic of many cancers. We investigated whether putatively functional single nucleotide polymorphisms (SNPs) in genes related to CIN (CENPF, ESPL1, NEK2, PTTG1, ZWILCH, ZWINT) affect breast cancer (BC) risk and clinical outcome in a Swedish cohort of 749 incident BC cases with detailed clinical data and up to 15 years of follow-up and 1493 matched controls. As a main observation, carriers of the A allele of the CENPF SNP rs438034 had a worse BC-specific survival compared to the wild type genotype GG carriers (hazard ratio (HR) 2.65, 95% confidence interval (CI) 1.19-5.90), although they were less likely to have regional lymph node metastases (odds ratio (OR) 0.71, 95% CI 0.51-1.01) and tumours of stage II-IV (OR 0.73, 95% CI 0.54-0.99). As there is increasing evidence that CENPF is associated with poor prognosis in patients with primary BC, further independent studies are needed to clarify the importance of genetic variation in the CENPF gene in the clinic.
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| 8. |
- Campa, Daniele, et al.
(författare)
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Genetic variation in genes of the fatty acid synthesis pathway and breast cancer risk.
- 2009
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 118:3, s. 565-574
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Tidskriftsartikel (refereegranskat)abstract
- Fatty acid synthase (FAS) is the major enzyme of lipogenesis. It catalyzes the NADPH-dependent condensation of acetyl-CoA and malonyl-CoA to produce palmitic acid. Transcription of the FAS gene is controlled synergistically by the transcription factors ChREBP (carbohydrate response element-binding protein), which is induced by glucose, and SREBP-1 (sterol response element-binding protein-1), which is stimulated by insulin through the PI3K/Akt signal transduction pathway. We investigated whether the genetic variability of the genes encoding for ChREBP, SREBP and FAS (respectively, MLXIPL, SREBF1 and FASN) is related to breast cancer risk and body-mass index (BMI) by studying 1,294 breast cancer cases and 2,452 controls from the European Prospective Investigation on Cancer (EPIC). We resequenced the FAS gene and combined information of SNPs found by resequencing and SNPs from public databases. Using a tagging approach and selecting 20 SNPs, we covered all the common genetic variation of these genes. In this study we were not able to find any statistically significant association between the SNPs in the FAS, ChREBP and SREPB-1 genes and an increased risk of breast cancer overall and by subgroups of age, menopausal status, hormone replacement therapy (HRT) use or BMI. On the other hand, we found that two SNPs in FASN were associated with BMI.
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| 9. |
- Canzian, Federico, et al.
(författare)
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Genetic polymorphisms of the GNRH1 and GNRHR genes and risk of breast cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3).
- 2009
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Ingår i: BMC cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 9, s. 257-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Gonadotropin releasing hormone (GNRH1) triggers the release of follicle stimulating hormone and luteinizing hormone from the pituitary. Genetic variants in the gene encoding GNRH1 or its receptor may influence breast cancer risk by modulating production of ovarian steroid hormones. We studied the association between breast cancer risk and polymorphisms in genes that code for GNRH1 and its receptor (GNRHR) in the large National Cancer Institute Breast and Prostate Cancer Cohort Consortium (NCI-BPC3). METHODS: We sequenced exons of GNRH1 and GNRHR in 95 invasive breast cancer cases. Resulting single nucleotide polymorphisms (SNPs) were genotyped and used to identify haplotype-tagging SNPs (htSNPS) in a panel of 349 healthy women. The htSNPs were genotyped in 5,603 invasive breast cancer cases and 7,480 controls from the Cancer Prevention Study-II (CPS-II), European Prospective Investigation on Cancer and Nutrition (EPIC), Multiethnic Cohort (MEC), Nurses' Health Study (NHS), and Women's Health Study (WHS). Circulating levels of sex steroids (androstenedione, estradiol, estrone and testosterone) were also measured in 4713 study subjects. RESULTS: Breast cancer risk was not associated with any polymorphism or haplotype in the GNRH1 and GNRHR genes, nor were there any statistically significant interactions with known breast cancer risk factors. Polymorphisms in these two genes were not strongly associated with circulating hormone levels. CONCLUSION: Common variants of the GNRH1 and GNRHR genes are not associated with risk of invasive breast cancer in Caucasians.
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| 10. |
- Dossus, Laure, et al.
(författare)
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Polymorphisms of genes coding for ghrelin and its receptor in relation to anthropometry, circulating levels of IGF-I and IGFBP-3, and breast cancer risk a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC)
- 2008
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Ingår i: Carcinogenesis. - : Oxford University Press. - 0143-3334 .- 1460-2180. ; 29:7, s. 1360-1366
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Tidskriftsartikel (refereegranskat)abstract
- Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor, has two major functions: the stimulation of the growth hormone production and the stimulation of food intake. Accumulating evidence also suggests a role of ghrelin in cancer development. We conducted a case-control study on 1359 breast cancer cases and 2389 matched controls, nested within the European Prospective Investigation into Cancer and Nutrition, to examine the association of common genetic variants in the genes coding for ghrelin (GHRL) and its receptor (GHSR) with anthropometric measures, circulating insulin growth factor I (IGF-I) and insulin-like growth factor-binding protein 3 and breast cancer risk. Pair-wise tagging was used to select the 15 polymorphisms that represent the majority of common genetic variants across the GHRL and GHSR genes. A significant increase in breast cancer risk was observed in carriers of the GHRL rs171407-G allele (odds ratio: 1.2; 95% confidence interval: 1.0-1.4; P = 0.02). The GHRL single-nucleotide polymorphism rs375577 was associated with a 5% increase in IGF-I levels (P = 0.01). A number of GHRL and GHSR polymorphisms were associated with body mass index (BMI) and height (P between <0.01 and 0.04). The false-positive report probability (FPRP) approach suggests that these results are noteworthy (FPRP < 0.20). The results presented here add to a growing body of evidence that GHRL variations are associated with BMI. Furthermore, we have observed evidence for association of GHRL polymorphisms with circulating IGF-I levels and with breast cancer risk. These associations, however, might also be due to chance findings and further large studies are needed to confirm our results.
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