| 1. |
- Basu, Samar, et al.
(författare)
-
Cellular Expression of Cyclooxygenase, Aromatase, Adipokines, Inflammation and Cell Proliferation Markers in Breast Cancer Specimen
- 2015
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:10
-
Tidskriftsartikel (refereegranskat)abstract
- Current evidences suggest that expression of Ki67, cyclooxygenase (COX), aromatase, adipokines, prostaglandins, free radicals, beta-catenin and alpha-SMA might be involved in breast cancer pathogenesis. The main objective of this study was to compare expression/localization of these potential compounds in breast cancer tissues with tissues collected adjacent to the tumor using immunohistochemistry and correlated with clinical pathology. The breast cancer specimens were collected from 30 women aged between 49 and 89 years who underwent breast surgery following cancer diagnosis. Expression levels of molecules by different stainings were graded as a score on a scale based upon staining intensity and proportion of positive cells/area or individually. AdipoR1, adiponectin, Ob-R, leptin, COX-1, COX-2, aromatase, PGF(2a), F-2-isoprostanes and alpha-SMA were localised on higher levels in the breast tissues adjacent to the tumor compared to tumor specimens when considering either score or staining area whereas COX-2 and AdipoR2 were found to be higher considering staining intensity and Ki67 on score level in the tumor tissue. There was no significant difference observed on beta-catenin either on score nor on staining area and intensity between tissues adjacent to the tumor and tumor tissues. A positive correlation was found between COX-1 and COX-2 in the tumor tissues. In conclusion, these suggest that Ki67, COXs, aromatase, prostaglandin, free radicals, adipokines, beta-catenin and alpha-SMA are involved in breast cancer. These further focus the need of examination of tissues adjacent to tumor, tumor itself and compare them with normal or benign breast tissues for a better understanding of breast cancer pathology and future evaluation of therapeutic benefit.
|
|
| 2. |
- Basu, Samar, et al.
(författare)
-
Inflammatory F2-isoprostane, prostaglandin F2α, pentraxin 3 levels and breast cancer risk : The Swedish Mammography Cohort
- 2016
-
Ingår i: Prostaglandins, Leukotrienes and Essential Fatty Acids. - : Elsevier BV. - 0952-3278 .- 1532-2823. ; 113, s. 28-32
-
Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Breast cancer is a common cancer among women. Identifying cellular participation of F2-isoprostane, prostaglandin F2α (PGF2α) and pentraxin 3 (PTX3) in cancer we evaluated whether their prediagnostic systemic levels that originate from different inflammatory pathways were associated with breast cancer risk.METHODS: Seventy-eight breast cancer cases diagnosed after blood collection and 797 controls from the Swedish Mammography Cohort were analysed for urinary F2-isoprostane, PGF2α and plasma PTX3 levels.RESULTS: None of the biomarkers investigated were significantly associated with breast cancer risk. However, there was the suggestion of an inverse association with PTX3 with multivariable adjusted ORs (95% CI) of 0.56 (95% CI=0.29-1.06) and 0.67 (95% CI=0.35-1.28) for the second and third tertiles, respectively (ptrend=0.20). No associations were observed between F2-isoprostane (OR=0.87; 95% CI=0.48-1.57; ptrend=0.67) and PGF2α metabolite (OR=1.03; 95% CI=0.56-1.88; ptrend=0.91) comparing the top to bottom tertiles.CONCLUSIONS: The systemic levels of F2-isoprostane, PGF2α and PTX3 witnessed in women who later developed breast cancer may not provide prognostic information regarding tumor development in spite of their known involvement in situ cellular context. These observations may indicate that other mechanisms exist in controlling cellular formation of F2-isoprostane, PGF2α and PTX3 and their systemic availability in breast cancer patients.
|
|
| 3. |
- Basu, Samar, et al.
(författare)
-
Is There any Role for Serum Cathepsin S, CRP levels on Prognostic Information in Breast Cancer? : The Swedish Mammography Cohort
- 2015
-
Ingår i: Antioxidants and Redox Signaling. - : Mary Ann Liebert Inc. - 1523-0864 .- 1557-7716. ; 23:16, s. 1298-1302
-
Tidskriftsartikel (refereegranskat)abstract
- Breast cancer is the most common cancer among women, and both low-grade inflammation and cathepsins might have important roles in breast cancer. We questioned whether prediagnostic circulating levels of C-reactive protein (CRP), cathepsin B and cathepsin S were associated with breast cancer risk. Sixty-nine incident breast cancer cases diagnosed after blood collection and 719 controls from the Swedish Mammography Cohort were analysed for systemic CRP, cathepsin B and cathepsin S. Cathepsin S and inflammation (hsCRP) adjusted cathepsin S were inversely associated with breast cancer risk (cathepsin S: OR for top vs. bottom tertile = 0.46; 95% CI = 0.23-0.92; Ptrend = 0.02; hsCRP adjusted cathepsin S: OR of 0.44; 95% CI = 0.22-0.87; Ptrend = 0.02). hsCRP was significantly associated with increased breast cancer risk (OR for top vs. bottom tertile= 2.01; 95% CI = 1.02-3.95; Ptrend = 0.04). No significant association was observed between cathepsin B and breast cancer risk (OR for top vs. bottom tertile= 0.67; 95% CI = 0.32-1.40; Ptrend = 0.30). These observations lead to hypothesis that levels of cathepsin S and hsCRP observed in women who later developed breast cancer may provide prognostic information regarding tumor development and need to be evaluated in prospective studies.
|
|
| 4. |
- Basu, Samar, et al.
(författare)
-
Ozone exposure effect on systemic prostaglandin F-2 alpha in rat plasma and urine may not reveal pulmonary damage through inflammation
- 2017
-
Ingår i: Prostaglandins, Leukotrienes and Essential Fatty Acids. - : Elsevier BV. - 0952-3278 .- 1532-2823. ; 126, s. 79-83
-
Tidskriftsartikel (refereegranskat)abstract
- The acute ozone induced lung injury model has been widely used to explore injury and repair processes induced by oxidant overload. The current study evaluated acute ozone exposure effects on prostaglandin F-2 alpha (PGF(2 alpha)) in male Fischer rat plasma and urine with the hypothesis that ozone may induce an inflammatory response in the body that can be measured by the induction of PGF2 alpha. That might then lead to the identification of potential marker for acute lung injury through systemic inflammation. The time and dose-dependent effects of ozone exposure on the plasma and urinary levels of a major PGF(2 alpha) metabolite15-keto-dihydro-PGF(2 alpha) were determined using a radioimmunoassay. No statistically significant differences in the PGF(2 alpha) metabolite were found between the control and the experimental groups at either ozone exposure dose (2 ppm and 5 ppm) or any time point (2 h, 7 h and 16 h) post exposure for plasma and at 7 different post exposure time points (between 2 and 80 h) for urine. It is concluded that acute ozone exposure does not cause changes in plasma and urinary PGF(2 alpha), and therefore their measurement in plasma and urine may not be used to reveal pulmonary inflammation and damage by ozone.
|
|
| 5. |
- Ekström, Eva-Charlotte, et al.
(författare)
-
Effects of prenatal micronutrient and early food supplementation on metabolic status of the offspring at 4.5 years of age. The MINIMat randomized trial in rural Bangladesh.
- 2016
-
Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 45:5, s. 1656-1667
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Fetal nutritional insults may alter the later metabolic phenotype. We hypothesized that early timing of prenatal food supplementation and multiple micronutrient supplementation (MMS) would favourably influence childhood metabolic phenotype.METHODS: Pregnant women recruited 1 January to 31 December 2002 in Matlab, Bangladesh, were randomized into supplementation with capsules of either 30 mg of iron and 400 μg of folic acid, 60 mg of iron and 400 μg of folic acid, or MMS containing a daily allowance of 15 micronutrients, and randomized to food supplementation (608 kcal) either with early invitation (9 weeks' gestation) or usual invitation (at 20 weeks). Their children (n = 1667) were followed up at 4.5 years with assessment of biomarkers of lipid and glucose metabolism, inflammation and oxidative stress.RESULTS: Children in the group with early timing of food supplementation had lower cholesterol (difference -0.079 mmol/l, 95% confidence interval (CI) -0.156; -0.003), low-density lipoprotein (LDL) (difference -0.068 mmol/l, 95% CI -0.126; -0.011) and ApoB levels (difference -0.017 g/l, 95% CL -0.033; -0.001). MMS supplementation resulted in lower high-density lipoprotein (HDL) (difference -0.028 mmol/l, 95% CL -0.053; -0.002), lower glucose (difference -0.099 mmol/l, 95% CL -0.179; -0.019) and lower insulin-like growth factor 1 (IGF-1) (difference on log scale -0.141 µg/l, 95% CL -0.254; -0.028) than 60 mg iron and 400 μg folic acid. There were no effects on markers of inflammation or oxidative stress.CONCLUSIONS: Findings suggest that in a population where malnutrition is prevalent, nutrition interventions during pregnancy may modify the metabolic phenotype in the young child that could have consequences for later chronic disease risks.
|
|
| 6. |
- Halvorsen, Peter, et al.
(författare)
-
Neural injury after use of vasopressin and adrenaline during porcine cardiopulmonary resuscitation
- 2015
-
Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 120:1, s. 11-19
-
Tidskriftsartikel (refereegranskat)abstract
- Background. Our aim was to investigate cerebral and cardiac tissue injury subsequent to use of vasopressin and adrenaline in combination compared with vasopressin alone during cardiopulmonary resuscitation (CPR). Methods. In a randomized, prospective, laboratory animal study 28 anesthetized piglets were subject to a 12-min untreated cardiac arrest and subsequent CPR. After 1 min of CPR, 10 of the piglets received 0.4 U/kg of arg(8)-vasopressin (V group), and 10 piglets received 0.4 U/kg of arg(8)-vasopressin, 1 min later followed by 20 mu g/kg body weight of adrenaline, and another 1 min later continuous administration (10 mu g/kg/min) of adrenaline (VA group). After 8 min of CPR, the piglets were defibrillated and monitored for another 3 h. Then they were killed and the brain immediately removed pending histological analysis. Results. During CPR, the VA group had higher mean blood pressure and cerebral cortical blood flow (CCBF) but similar coronary perfusion pressure. After restoration of spontaneous circulation there was no difference in the pressure variables, but CCBF tended to be (36% +/- 16%) higher in the V group. Neuronal injury and signs of a disrupted blood-brain barrier (BBB) were greater, 20% +/- 4% and 21% +/- 4%, respectively, in the VA group. In a background study of repeated single doses of adrenaline every third minute after 5 min arrest but otherwise the same protocol, histological measurements showed even worse neural injury and disruption of the BBB. Conclusion. Combined use of vasopressin and adrenaline caused greater signs of cerebral and cardiac injury than use of vasopressin alone during experimental cardiopulmonary resuscitation.
|
|
| 7. |
- Hansson, Patrik, et al.
(författare)
-
Habitual high intake of fatty fish is related to lower levels of F2-isoprostanes in healthy females
- 2015
-
Ingår i: Nutrition. - : Elsevier BV. - 0899-9007 .- 1873-1244. ; 31:6, s. 847-852
-
Tidskriftsartikel (refereegranskat)abstract
- Objective The aim of this study was to determine whether habitual dietary intake of fatty fish, whole grains, fruits and vegetables, or a combination of them all, is associated with oxidative stress levels, measured as urine concentration of 8-iso-prostaglandin F2α (8-iso-PGF2α) in healthy women. Methods Eighty-one participants were included in this cross-sectional study. Mean age of the women was 26.1 ± 6.2 (mean ± SD) years and mean body mass index (BMI) was 22.4 ± 3.0 kg/m2. The concentration of 8-iso-PGF2α was determined in urine, and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) levels were determined in blood. Participants' habitual fish, whole grain, fruit, and vegetable intake was estimated from a food frequency questionnaire. Results In the multivariate analysis, there was a significant inverse association between 8-iso-PGF2α and high fatty fish intake (P < 0.001). Fatty fish intake was positively correlated to serum phospholipid concentrations of EPA (P = 0.001) and DHA (P = 0.002). A borderline effect of DHA was seen on 8-iso-PGF2α, but higher serum phospholipid concentrations of fatty acids were generally not related to lower F2-isoprostane levels. No overall effect from whole grains or fruits and vegetables was seen. Conclusions The results indicate that high intake of fatty fish is related to lower levels of oxidative stress, but high levels of ω-3 fatty acids in intake may not alone explain the effect. High habitual intake of whole grains or fruits and vegetables did not seem to affect the F2-isoprostane level.
|
|
| 8. |
- Harris, Holly, et al.
(författare)
-
Soluble vascular endothelial growth factor receptors 2 (sVEGFR-2) and 3 (sVEGFR-3) and breast cancer risk in the Swedish Mammography Cohort
- 2016
-
Ingår i: International Journal of Molecular Epidemiology and Genetics. - 1948-1756. ; 7:1, s. 81-86
-
Tidskriftsartikel (refereegranskat)abstract
- Vascular endothelial growth factor (VEGF) is a signalling protein that has been established as a contributor to tumor angiogenesis, and expression of VEGF and its soluble receptors (sVEGFR2 and sVEGFR3) have been demonstrated in breast cancer cells. However, no prospective studies have examined the association between prediagnostic sVEGFR levels and breast cancer risk. We conducted a prospective case-control study nested within the Swedish Mammography Cohort examining the association between sVEGFR2 and 3 levels and breast cancer risk. The analysis included 69 incident breast cancer cases diagnosed after blood collection and 719 controls. Logistic regression models were used to calculate odds ratios and 95% confidence intervals. After adjustment for breast cancer risk factors, sVEGFR2 levels were associated with breast cancer risk (OR=1.28; 95% CI=1.06-1.56 per 1000 ng/L increase in concentration) while sVEGFR3 levels were not related to such risk (OR=1.00; 95% CI=0.93-1.07). Our results suggest that sVEGFR2 levels may be positively associated with breast cancer risk, however future studies with larger case groups are necessary to confirm this association.
|
|
| 9. |
- Helmersson-Karlqvist, Johanna, et al.
(författare)
-
Prostaglandin F2α formation is associated with mortality in a Swedish community-based cohort of older males
- 2015
-
Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 36:4, s. 238-243
-
Tidskriftsartikel (refereegranskat)abstract
- AIMS: An increasing number of clinical studies highlight the importance of the inflammatory mediator prostaglandin F2α (PGF2α). Prostaglandin F2α activity has been suggested to play pivotal roles in the development of cardiovascular diseases and cancer. However, whether systemic PGF2α concentrations may signal mortality is unknown. The aim was to evaluate in vivo PGF2α formation, by measuring urinary 15-keto-dihydro-PGF2α, and mortality risk in a community setting.METHODS AND RESULTS: Urinary 15-keto-dihydro-PGF2α was measured in a Swedish population of 670 men (aged 77-78 years) and the participants were followed up for a median of 9.7 years (383 died, among them 156 of cardiovascular causes and 102 of cancer). In Cox regression models, urinary 15-keto-dihydro-PGF2α was significantly associated with cardiovascular mortality [multivariate hazard ratio (HR) for 1 SD increase of urinary 15-keto-dihydro-PGF2α: 1.18; 95% CI:1.04-1.34; P = 0.01) independent of established cardiovascular risk factors including C-reactive protein. Urinary 15-keto-dihydro-PGF2α was also independently associated with total mortality (multivariate HR for 1 SD increase of urinary 15-keto-dihydro-PGF2α: 1.11; 95% CI: 1.01-1.21; P = 0.03). The combination of 15-keto-dihydro-PGF2α concentrations above the median and high serum high-sensitive C-reactive protein (>3 mg/L) was independently associated with a two-fold increased risk of cancer and total mortality (P = 0.02 and P < 0.001, respectively).CONCLUSION: This is the first study to show that the inflammatory mediator PGF2α was independently associated with mortality and specifically cardiovascular mortality 10 years later. The results are in line with the emerging evidence of the importance of the inflammatory mediator PGF2α in fatal cardiovascular disease.
|
|
| 10. |
- Kadiiska, Maria B., et al.
(författare)
-
Biomarkers of oxidative stress study VI. Endogenous plasma antioxidants fail as useful biomarkers of endotoxin-induced oxidative stress
- 2015
-
Ingår i: Free Radical Biology & Medicine. - : Elsevier BV. - 0891-5849 .- 1873-4596. ; 81, s. 100-106
-
Tidskriftsartikel (refereegranskat)abstract
- This is the newest report in a series of publications aiming to identify a blood-based antioxidant biomarker that could serve as an in vivo indicator of oxidative stress. The goal of the study was to test whether acutely exposing Gottingen mini pigs to the endotoxin lipopolysaccharide (LPS) results in a loss of antioxidants from plasma. We set as a criterion that a significant effect should be measured in plasma and seen at both doses and at more than one time point Animals were injected with two doses of LPS at 2.5 and 514/kg iv. Control plasma was collected from each animal before the LPS injection. After the LPS injection, plasma samples were collected at 2, 16, 48, and 72 h. Compared with the controls at the same time point, statistically significant losses were not found for either dose at multiple time points in any of the following potential markers: ascorbic acid, tocopherols (alpha, delta, gamma), ratios of GSH/GSSG and cysteine/cystine, mixed disulfides, and total antioxidant capacity. However, uric acid, total GSH, and total Cys were significantly increased, probably because LPS had a harmful effect on the liver. The leakage of substances from damaged cells into the plasma may have increased plasma antioxidant concentrations, making changes difficult to interpret Although this study used a mini-pig animal model of LPS-induced oxidative stress, it confirmed our previous findings in different rat models that measurement of antioxidants in plasma is not useful for the assessment of oxidative damage in vivo.
|
|
