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Sökning: WFRF:(Tognon Gianluca 1976)

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  • Bottone, Maria Grazia, et al. (författare)
  • Multiple effects of paclitaxel are modulated by a high c-myc amplification level.
  • 2003
  • Ingår i: Experimental cell research. - 0014-4827. ; 290:1, s. 49-59
  • Tidskriftsartikel (refereegranskat)abstract
    • Paclitaxel affects microtubule stability by binding to beta-tubulin, thus leading to cell accumulation in the G(2)/M phase, polyploidization, and apoptosis. Because both cell proliferation and apoptosis could be somehow regulated by the protooncogene c-myc, in this work we have investigated whether the c-myc amplification level could modulate the multiple effects of paclitaxel. To this aim, paclitaxel was administered to SW613-12A1 and -B3 human colon carcinoma cell lines (which are characterized by a high and low c-myc endogenous amplification level, respectively), and to the B3mycC5 cell line, with an enforced exogenous expression of c-myc copies. In this experimental system, we previously demonstrated that a high endogenous/exogenous level of amplification of c-myc enhances serum deprivation- and DNA damage-induced apoptosis. Accordingly, the present results indicate that a high c-myc amplification level potentiates paclitaxel cytotoxicity, confers a multinucleated phenotype, and promotes apoptosis to a great extent, thus suggesting that c-myc expression level is relevant in modulating the cellular responses to paclitaxel. We have recently shown in HeLa cells that the phosphorylated form of c-Myc accumulates in the nucleus, as distinct nucleolar and extranucleolar spots; here, we demonstrated that, after the treatment with paclitaxel, phosphorylated c-Myc undergoes redistribution, becoming diffused in the nucleoplasm.
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  • D'Incalci, Maurizio, et al. (författare)
  • Unique features of the mode of action of ET-743.
  • 2002
  • Ingår i: The oncologist. - 1083-7159. ; 7:3, s. 210-6
  • Forskningsöversikt (refereegranskat)abstract
    • This paper describes the current knowledge of the primary mode of action of a natural product, ecteinascidin 743 (ET-743), derived from the marine tunicate Ecteinascidia turbinata. ET-743 was initially selected for preclinical development because of its potent antitumor activity observed against several human solid tumor types. In vitro, the drug is cytotoxic in the nanomolar range, and in the case of some very sensitive cell lines, in the picomolar range. The large potency differences observed among several solid tumor types indicate that this compound possesses some tumor selectivity, but the molecular basis of these differential effects remains to be elucidated. The present studies were undertaken to evaluate the mechanism of action of ET-743 in this context. The available information on ET-743 binding to DNA and its effects on transcriptional regulation point to a unique behavior of this drug, as it independently affects specific gene transcription in a promoter-dependent way. In addition, ET-743 shows a peculiar pattern of selectivity in cells with different defects in their DNA-repair pathways. These results highlight a unique property of ET-743, possibly explaining why it possesses antitumor activity against tumors that are refractory to standard anticancer drugs, all of which certainly act by mechanisms that are different from that of ET-743.
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  • Erba, E, et al. (författare)
  • Effect of Aplidin in acute lymphoblastic leukaemia cells.
  • 2003
  • Ingår i: British journal of cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 89:4, s. 763-73
  • Tidskriftsartikel (refereegranskat)abstract
    • The cytotoxic effect of Aplidin was investigated on fresh leukaemia cells derived from children with B-cell-precursor (BCP) acute lymphoblastic leukaemia (ALL) by using stromal-layer culture system and on four cell lines, ALL-PO, Reh, ALL/MIK and TOM-1, derived from patients with ALL with different molecular genetic abnormalities. In ALL cell lines Aplidin was cytotoxic at nanomolar concentrations. In the ALL cell lines the drug-induced cell death was clearly related to the induction of apoptosis and appeared to be p53-independent. Only in ALL-PO 20 nM Aplidin treatment caused a block of vascular endothelial growth factor (VEGF) secretion and downregulation of VEGF-mRNA, but Aplidin cytotoxicity does not seem to be related to VEGF inhibition since the sensitivity of ALL-PO cells to Aplidin is comparable to that observed for the other cells used. Aplidin induced a G(1) and a G(2) M block in ALL cell lines. In patient-derived leukaemia cells, Aplidin induced a strong cytotoxicity evidenced in a stroma-supported immunocytometric assay. Cells from children with genetic abnormalities such as t(9;22) and t(4;11) translocations, associated with an inferior treatment outcome, were sensitive to Aplidin to the same extent as that observed in other BCP-ALL cases. Aplidin exerted a strong cell killing effect (>88%) against primary culture cells from five relapsed ALL cases, at concentrations much lower than those reported to be achieved in plasma of patients receiving Aplidin at recommended doses. Taken together these data suggest that Aplidin could be a new anticancer drug to be investigated in ALL patients resistant to available therapy.
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  • Finardi, Corrado, et al. (författare)
  • Is "junk food" an "healthy concept"? From policy making back to science
  • 2014
  • Ingår i: British Food Journal. - 0007-070X. ; 116:8, s. 1222-1232
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose – The term “junk food” is for the most part currently used in the widest political and media debate, without reference to something tangible. The purpose of this paper is to pinpoint the delicate issues involved in moving towards a trans-national, unified, consensual definition of the term “junk food”, including social, economic, cultural, nutritional and methodological problems. Design/methodology/approach – Departing from the work done by international bodies (WHO, FAO-Codex Alimentarius, OECD, EFSA and European Commission) authors descriptively investigate possible background elements able to frame the surrounding debate about “junk food” (“nutrient profiles”, labelling provisions, institutional aspects, etc.). Findings – Presently there is a lack of a global consensus and of scientific basis to define clearly what constitutes “junk food” either on regional areas or globally. Despite of good metrics able to classify foods according to their nutritional quality, policy making relies yet on the concept that only diets or single nutrients can be focused as “good or bad”. Practical implications – A “junk food” taxonomy could be helpful to harmonize trade policies in internal markets (i.e. the EU) and at global level; but also to gain a wider social support for “hard” policy measures intending to counteract non-communicable-diseases (NCDs), and more generally, obesity and overweight. Social implications – A clear basis for “junk food” definition could be the first step to introduce otherwise controversial and easily opposable public health policies and campaigns, due to private interests of the different stakeholders. Even consumers may perceive food policies (in the sake of “food taxes” or “traffic light labelling”) as unfair, whereas not robust scientific ground has been previously given at the highest possible level. Originality/value – The value of this descriptive paper consists in addressing the shortcomings of global and regional nutritional policies framework in front of the emerging trend of “globesity”. Conclusions stress the need to find support for broader food policies (labelling, taxes, education, bans, etc.) which currently are on the rise but lack fundamental aspects of scientific and hence social support.
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  • Finardi, C., et al. (författare)
  • "Is 'junk food' an 'healthy' concept?" the challenges of the current debate From policy making back to science
  • 2014
  • Ingår i: British Food Journal. - : Emerald. - 0007-070X. ; 116:8, s. 1222-1232
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose - The term "junk food" is for the most part currently used in the widest political and media debate, without reference to something tangible. The purpose of this paper is to pinpoint the delicate issues involved in moving towards a trans-national, unified, consensual definition of the term "junk food", including social, economic, cultural, nutritional and methodological problems. Design/methodology/approach - Departing from the work done by international bodies (WHO, FAO-Codex Alimentarius, OECD, EFSA and European Commission) authors descriptively investigate possible background elements able to frame the surrounding debate about "junk food"("nutrient profiles", labelling provisions, institutional aspects, etc.). Findings - Presently there is a lack of a global consensus and of scientific basis to define clearly what constitutes "junk food" either on regional areas or globally. Despite of good metrics able to classify foods according to their nutritional quality, policy making relies yet on the concept that only diets or single nutrients can be focused as "good or bad". Practical implications - A "junk food" taxonomy could be helpful to harmonize trade policies in internal markets (i.e. the EU) and at global level; but also to gain a wider social support for "hard" policy measures intending to counteract non-communicable-diseases (NCDs), and more generally, obesity and overweight. Social implications - A clear basis for "junk food" definition could be the first step to introduce otherwise controversial and easily opposable public health policies and campaigns, due to private interests of the different stakeholders. Even consumers may perceive food policies (in the sake of "food taxes" or "traffic light labelling") as unfair, whereas not robust scientific ground has been previously given at the highest possible level. Originality/value - The value of this descriptive paper consists in addressing the shortcomings of global and regional nutritional policies framework in front of the emerging trend of "globesity". Conclusions stress the need to find support for broader food policies (labelling, taxes, education, bans, etc.) which currently are on the rise but lack fundamental aspects of scientific and hence social support.
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  • González-Gil, Esther María, et al. (författare)
  • Prospective associations between dietary patterns and high sensitivity C-reactive protein in European children: the IDEFICS study.
  • 2018
  • Ingår i: European journal of nutrition. - : Springer Science and Business Media LLC. - 1436-6215 .- 1436-6207. ; 57:4, s. 1397-1407
  • Tidskriftsartikel (refereegranskat)abstract
    • This prospective study explores high sensitivity C-reactive protein (hs-CRP) levels in relation to dietary patterns at two time points in European children.Out of the baseline sample of the IDEFICS study (n=16,228), 4020 children, aged 2-9 years at baseline, with available hs-CRP levels and valid data from a food frequency questionnaire (FFQ) at baseline (T0) and 2 years later (T1) were included. K-means clustering algorithm based on the similarities between relative food consumption frequencies of the FFQ was applied. hs-CRP was dichotomized according to sex-specific cutoff points. Multilevel logistic regression was performed to assess the relationship between dietary patterns and hs-CRP adjusting for covariates.Three consistent dietary patterns were found at T0 and T1: 'animal protein and refined carbohydrate', 'sweet and processed' and 'healthy'. Children allocated to the 'protein' and 'sweet and processed' clusters at both time points had significantly higher odds of being in the highest category of hs-CRP (OR 1.47; 95% CI 1.03-2.09 for 'animal protein and refined carbohydrate' and OR 1.44; 95% CI 1.08-1.92 for 'sweet and processed') compared to the 'healthy' cluster. The odds remained significantly higher for the 'sweet and processed' pattern (OR 1.39; 95% CI 1.05-1.84) when covariates were included.A dietary pattern characterized by frequent consumption of sugar and processed products and infrequent consumption of vegetables and fruits over time was independently related with inflammation in European children. Efforts to improve the quality of the diet in childhood may prevent future diseases related with chronic inflammation.
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  • Hunsberger, Monica, 1973, et al. (författare)
  • Low fat diets in obesity management and weight control.
  • 2014
  • Ingår i: Managing and preventing obesity: behavioural factors and dietary interventions.. - : Woodhead Publishing..
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)
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  • Mehlig, Kirsten, 1964, et al. (författare)
  • The association between plasma homocysteine and coronary heart disease is modified by the MTHFR 677C>T polymorphism.
  • 2013
  • Ingår i: Heart (British Cardiac Society). - : BMJ. - 1468-201X .- 1355-6037. ; 99:23, s. 1761-1765
  • Tidskriftsartikel (refereegranskat)abstract
    • An elevated level of total plasma homocysteine (tHcy) has been associated with risk of coronary heart disease (CHD). The level of tHcy is affected by lifestyle, in addition to genetic predisposition. The methylene tetrahydrofolate reductase (MTHFR) 677C>T polymorphism (rs1801133) is among the strongest genetic predictors of tHcy. We examined whether the association between tHcy and CHD is modified by the MTHFR 677C>T polymorphism.
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  • Soldani, C, et al. (författare)
  • Poly(ADP-ribose) polymerase cleavage during apoptosis: when and where?
  • 2001
  • Ingår i: Experimental cell research. - : Elsevier BV. - 0014-4827. ; 269:2, s. 193-201
  • Tidskriftsartikel (refereegranskat)abstract
    • Poly(ADP-ribose) polymerase-1 (PARP-1) plays the active role of "nick sensor" during DNA repair and apoptosis, when it synthesizes ADP-ribose from NAD(+) in the presence of DNA strand breaks. Moreover, PARP-1 becomes a target of apoptotic caspases, which originate two proteolytic fragments of 89 and 24 kDa. The precise relationship between PARP-1 activation and degradation during apoptosis is still a matter of debate. In human Hep-2 cells driven to apoptosis by actinomycin D, we have monitored PARP-1 activity by the mAb 10H, which is specific for the ADP-ribose polymers, and we have observed that poly(ADP-ribose) synthesis is a very early response to the apoptotic stimulus. The analysis of the presence and fate of the p89 proteolytic fragment revealed that PARP-1 proteolysis by caspases is concomitant with poly(ADP-ribose) synthesis and that p89 migrates from the nucleus into the cytoplasm in late apoptotic cells with advanced nuclear fragmentation.
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  • Tavecchio, Michele, et al. (författare)
  • Multi-parametric flow cytometric cell cycle analysis using TO-PRO-3 iodide (TP3): detailed protocols.
  • 2008
  • Ingår i: Acta histochemica. - : Elsevier BV. - 0065-1281. ; 110:3, s. 232-44
  • Tidskriftsartikel (refereegranskat)abstract
    • TO-PRO-3 iodide (TP3), a monomeric cyanine nucleic acid stain with a peak absorbance at 642 nm and emission at 661 nm, is best excited by a helium-neon (HeNe) laser (633nm). It was tested in monocytes and different cell lines under conditions of different fixatives, dye concentrations, labeling kinetics and RNAse concentrations for mono-, bi- and tri-parametric flow cytometric cell cycle analysis to establish the best protocol for DNA analysis in terms of G1 peak CV, G2/G1 ratio and minimal amount of debris. A linear increase in G1 peak position was found from 0.1 to 2 microM TP3 concentrations. Fixatives 70% ethanol or 1% methanol-free formaldehyde, followed by 70% ethanol, resulted in the best DNA histograms. Although different protocols were found to be cell-type specific, in general, excellent results were obtained with 30 min incubation with 0.5 microM TP3 plus RNAse in almost all cell lines tested. These data show that TP3 is an alternative method to propidium iodide (PI), the most commonly used DNA-specific probe in flow cytometry. The most important advantage of using TP3 in combination with other fluorochromes, such as fluorescein isothiocyanate (FITC) or phycoerythrin (PE) in bi- or tri-parametric flow cytometric analysis, is that there is no need for fluorescence compensation for the TP3 signals.
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  • Tognon, Gianluca, 1976, et al. (författare)
  • Adherence to a Mediterranean-like dietary pattern in children from eight European countries. The IDEFICS study.
  • 2014
  • Ingår i: International journal of obesity (2005). - : Springer Science and Business Media LLC. - 1476-5497 .- 0307-0565. ; 38 Suppl 2
  • Tidskriftsartikel (refereegranskat)abstract
    • Despite documented benefits of a Mediterranean-like dietary pattern, there is a lack of knowledge about how children from different European countries compare with each other in relation to the adherence to this pattern. In response to this need, we calculated the Mediterranean diet score (MDS) in 2-9-year-old children from the Identification and prevention of dietary- and lifestyle-induced health effects in children and infants (IDEFICS) eight-country study.
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  • Tognon, Gianluca, 1976, et al. (författare)
  • Are segmental MF-BIA scales able to reliably assess fat mass and lean soft tissue in an elderly Swedish population?
  • 2015
  • Ingår i: Experimental Gerontology. - : Elsevier BV. - 0531-5565 .- 1873-6815. ; 72, s. 239-243
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and aims The assessment of body composition is an important measure to monitor the process of healthy aging and detect early signs of disease. Dual X-ray absorptiometry (DXA) is considered a valid technique for the assessment of body composition but is confined to the clinical environment. Multi-frequency bio-electrical impedance analysis (MF-BIA) might be a versatile alternative to DXA. We aimed to assess whether a segmental MF-BIA scale can be an accurate and reliable tool for the monitoring of body composition in the elderly and whether the presence of metallic prostheses can influence the agreement between the two techniques. Subjects and methods Weight and height were measured in 92 healthy subjects (53 women) aged 80–81 years from the H70 Gerontological and Geriatric study in Gothenburg. Total and segmental fat mass (FM) and lean soft tissue (LST) were estimated by DXA (Lunar Prodigy, Scanex, Sweden) and segmental MF-BIA (MC-180MA, Tanita, Japan). Bland–Altman analyses were performed to assess the agreement between the two techniques. The prediction of DXA-FM by MF-BIA was compared to that of the body mass index (BMI). Results and discussion MF-BIA showed a significant underestimation of FM and an overestimation of LST that was larger in men than in women. Smaller but significant deviations were found for appendicular LST and SMM. MF-BIA was not superior to BMI at predicting DXA-FM. The lack of agreement between MF-BIA and DXA was not due to the presence of metal prostheses or diagnoses such as hypertension and edema. The prediction equations applied by the device used in this study should be adapted to the elderly population and details about the reference population(s) should be disclosed.
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  • Tognon, Gianluca, 1976 (författare)
  • Chimica Nociva
  • 2011
  • Bok (övrigt vetenskapligt/konstnärligt)abstract
    • This book is aimed to disseminate and raise awareness of the delicate topic of toxic chemicals and their effects on human health. The book adopts a simple and accessible language, even tough it includes some technical details on toxicology. The volume is divided into three sections, the first one is a description of some important toxic chemicals. The second part describes toxics' health effects on human health. The third section explains the European REACH legislation on toxic chemicals.
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  • Tognon, Gianluca, 1976, et al. (författare)
  • Comparison of Apolipoprotein (apoB/apoA-I) and Lipoprotein (Total Cholesterol/HDL) Ratio Determinants. Focus on Obesity, Diet and Alcohol Intake.
  • 2012
  • Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 7:7
  • Tidskriftsartikel (refereegranskat)abstract
    • The ratio between apolipoprotein B and apolipoprotein A-I (apoB/apoA-I) has been suggested to be a powerful and more accurate predictor of future cardiovascular disease risk than total cholesterol and HDL cholesterol. Since diet and lifestyle can directly influence dyslipidemia, it is of interest to identify modifiable factors that are associated with high levels of the apolipoprotein ratio and if they can have a different association with a more traditional indicator of cardiovascular risk such as total cholesterol/HDL. The relationship between obesity and dyslipidemia is established and it is of interest to determine which factors can modify this association. This study investigated the cross-sectional association of obesity, diet and lifestyle factors with apoB/apoA-I and total cholesterol/HDL respectively, in a Swedish population of 2,907 subjects (1,537 women) as part of the INTERGENE study. The apolipoprotein and lipoprotein ratios were highly correlated, particularly in women, and obesity was strongly associated with both. Additionally, age, cigarette smoking and alcohol intake were important determinants of these ratios. Alcohol was the only dietary factor that appreciably attenuated the association between obesity and each of the ratios, with a stronger attenuation in women. Other dietary intake and lifestyle-related factors such as smoking status and physical activity had a lower effect on this association. Because the apolipoprotein and lipoprotein ratios share similar diet and lifestyle determinants as well as being highly correlated, we conclude that either of these ratios may be a sufficient indicator of dyslipidemia.
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  • Tognon, Gianluca, 1976, et al. (författare)
  • Dairy product intake and mortality in a cohort of 70-year-old Swedes: a contribution to the Nordic diet discussion
  • 2018
  • Ingår i: European Journal of Nutrition. - : Springer Science and Business Media LLC. - 1436-6207 .- 1436-6215. ; 57:8, s. 2869-2876
  • Tidskriftsartikel (refereegranskat)abstract
    • © 2017 The Author(s) Introduction: Conflicting results in the literature exist on the role of dairy products in the context of a Nordic Healthy Diet (NHD). Two recent Swedish studies indicate both negative and positive associations with total mortality when comparing key dairy products. There is no consensus about how to include these foods into the NHD. Purpose: To study consumption of cheese and milk products (milk, sour milk and unsweetened yoghurt) by 70-year-old Swedes in relation to all-cause mortality. Methods: Cox proportional hazard models, adjusted for potential confounders and stratified by follow-up duration, were used to assess the prediction of all-cause mortality by the above foods. The associations of fat from cheese and milk products with mortality were tested in separate models. Results: Cheese intake inversely predicted total mortality, particularly at high protein intakes, and this association decreased in strength with increasing follow-up time. Milk products predicted increased mortality with stable HRs over follow-up. The association between milk products and mortality was strongly influenced by the group with the highest consumption. Fat from cheese mirrored the protective association of cheese intake with mortality, whereas fat from milk products predicted excess mortality, but only in an energy-adjusted model. Conclusion: Based on our results, it may be argued that the role of dairy products in the context of a Nordic healthy diet should be more clearly defined by disaggregating cheese and milk products and not necessarily focusing on dairy fat content. Future epidemiological research should consider dairy products as disaggregated food items due to their great diversity in health properties.
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  • Tognon, Gianluca, 1976, et al. (författare)
  • Does the Mediterranean diet predict longevity in the elderly? A Swedish perspective.
  • 2011
  • Ingår i: Age (Dordrecht, Netherlands). - : Springer Science and Business Media LLC. - 1574-4647 .- 0161-9152. ; 33:3, s. 439-50
  • Tidskriftsartikel (refereegranskat)abstract
    • Dietary pattern analysis represents a useful improvement in the investigation of diet and health relationships. Particularly, the Mediterranean diet pattern has been associated with reduced mortality risk in several studies involving both younger and elderly population groups. In this research, relationships between dietary macronutrient composition, as well as the Mediterranean diet, and total mortality were assessed in 1,037 seventy-year-old subjects (540 females) information. Diet macronutrient composition was not associated with mortality, while a refined version of the modified Mediterranean diet index showed a significant inverse association (HR=0.93, 95% CI: 0.89; 0.98). As expected, inactive subjects, smokers and those with a higher waist circumference had a higher mortality, while a reduced risk characterized married and more educated people. Sensitivity analyses (which confirmed our results) consisted of: exclusion of one food group at a time in the Mediterranean diet index, exclusion of early deaths, censoring at fixed follow-up time, adjusting for activities of daily living and main cardiovascular risk factors including weight/waist circumference changes at follow up. In conclusion, we can reasonably state that a higher adherence to a Mediterranean diet pattern, especially by consuming wholegrain cereals, foods rich in polyunsaturated fatty acids, and a limited amount of alcohol, predicts increased longevity in the elderly.
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  • Tognon, Gianluca, 1976 (författare)
  • Emerging Food Chemical Contaminants from Industry Pollution
  • 2013
  • Ingår i: European Journal of Risk Regulation. - 1867-299X. ; 4:1, s. 76-80
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • In May 2011, the illegal use of the plasticizer di(2-ethylhexyl) phthalate in clouding agents for use in foods and beverages was reported in Taiwan. This food scandal has caused shock and panic among the majority of Taiwanese people and has attracted international attention raising once again concern regarding the contamination of food by chemical toxic compounds.1 However, although these accidents cause a lot of concern, it is worth remembering that governments throughout the world are intensifying their efforts to improve food safety. In Europe in particular, food policy is based on high safety standards, aimed to protect and promote consumers’ health. EU legislation specifies that food containing a level of contaminants that is unacceptable from a public health viewpoint, cannot be put on the market. Currently, one of the great challenges in food safety is the control of risks associated with mixtures of contaminants, which are constantly changing. Food may be contaminated by chemical substances through production practices, packaging, transport, or storage. The contamination might also result from environmental pollution through contaminated air, water, soil, and accumulation in the food chain. Among the most prominent groups of emerging food contaminants, those from industrial sources (perfluorinated compounds (PFCs), polybrominated biphenyls (PBBs) and, partially, nanomaterials) cause particular concern. Many of these can be associated with severe damage to human health, for example some are suspected to be cancer promoters. Other compounds have been associated with endocrine disruptor effects, or can be accumulated and biomagnified through the food chain.
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  • Tognon, Gianluca, 1976, et al. (författare)
  • Induction of resistance to Aplidin in a human ovarian cancer cell line related to MDR expression.
  • 2005
  • Ingår i: Cancer biology & therapy. - 1538-4047. ; 4:12, s. 1325-30
  • Tidskriftsartikel (refereegranskat)abstract
    • Aplidin-resistant IGROV-1/APL cells were derived from the human ovarian cancer IGROV-1 cell line by exposing the cells to increasing concentration of Aplidin for eight months, starting from a concentration of 10 nM to a final concentration of 4 microM. IGROV-1/APL cell line possesses five fold relative resistance to Aplidin. IGROV-1/APL resistant cell line shows the typical MDR phenotype: (1) increased expression of membrane-associated P-glycoprotein, (2) cross-resistance to drugs like etoposide, doxorubicin, vinblastine, vincristine, taxol, colchicin and the novel anticancer drug Yondelis (ET-743). The Pgp inhibitor cyclosporin-A restored the sensitivity of IGROV-1/APL cells to Aplidin by increasing the drug intracellular concentration. The resistance to Aplidin was not due to the other proteins, such as LPR-1 and MRP-1, being expressed at the same level in resistant and parental cell line. The finding that cells over-expressing Pgp are resistant to Aplidin was confirmed in CEM/VLB 100 cells, that was found to be 5-fold resistant to Aplidin compared to the CEM parental cell line.
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  • Tognon, Gianluca, 1976, et al. (författare)
  • Nonfermented milk and other dairy products: associations with all-cause mortality 1,2
  • 2017
  • Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 105:6, s. 1502-1511
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: A positive association between nonfermented milk intake and increased all-cause mortality was recently reported, but overall, the association between dairy intake and mortality is inconclusive. Objective: We studied associations between intake of dairy products and all-cause mortality with an emphasis on nonfermented milk and fat content. Design: A total of 103,256 adult participants (women: 51.0%) from Northern Sweden were included (7121 deaths; mean follow-up: 13.7 y). Associations between all-cause mortality and reported intakes of nonfermented milk (total or by fat content), fermented milk, cheese, and butter were tested with the use of Cox proportional hazards models that were adjusted for age, sex, body mass index, smoking status, education, energy intake, examination year, and physical activity. To circumvent confounding, Mendelian randomization was applied in a subsample via the lactase LCT-13910 C/T single nucleotide polymorphism that is associated with lactose tolerance and milk intake. Results: High consumers of nonfermented milk (>= 2.5 times/d) had a 32% increased hazard (HR: 1.32; 95% CI: 1.18, 1.48) for all-cause mortality compared with that of subjects who consumed milk <= 1 time/wk. The corresponding value for butter was 11% (HR: 1.11; 95% CI: 1.07, 1.21). All nonfermented milk-fat types were independently associated with increased HRs, but compared with full-fat milk, HRs were lower in consumers of medium-and low-fat milk. Fermented milk intake (HR: 0.90; 95% CI: 0.86, 0.94) and cheese intake (HR: 0.93; 95% CI: 0.91, 0.96) were negatively associated with mortality. Results were slightly attenuated by lifestyle adjustments but were robust in sensitivity analyses. Mortality was not significantly associated with the LCT-13910 C/T genotype in the smaller subsample. The amount and type of milk intake was associated with lifestyle variables. Conclusions: In the present Swedish cohort study, intakes of nonfermented milk and butter are associated with higher all-cause mortality, and fermented milk and cheese intakes are associated with lower all-cause mortality. Residual confounding by lifestyle cannot be excluded, and Mendelian randomization needs to be examined in a larger sample.
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  • Tognon, Gianluca, 1976, et al. (författare)
  • The Mediterranean diet in relation to mortality and CVD: a Danish cohort study
  • 2014
  • Ingår i: British Journal of Nutrition. - 0007-1145 .- 1475-2662. ; 111:1, s. 151-159
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of the present study was to determine whether the Mediterranean Diet Score (MDS) is associated with reduced total mortality, cardiovascular incidence and mortality in a Danish population. Analyses were performed on 1849 men and women sampled during the 1982-83 Danish MONICA (MONItoring trends and determinants of Cardiovascular disease) population study, whose diet was assessed by means of a validated 7d food record. The adherence to a Mediterranean dietary pattern was calculated by three different scores: one based on a classification excluding ingredients from mixed dishes and recipes (score 1); another based on a classification including ingredients (score 2); the last one based on a variant of the latter including wine instead of alcohol intake (score 3). The association between these scores and, respectively, total mortality, cardiovascular incidence and mortality was tested by a Cox proportional hazards model adjusted for several potential confounders of the association. Generally, all three scores were inversely associated with the endpoints, although associations with score 1 did not reach statistical significance. Score 2 was inversely associated with total mortality (hazard ratio 0·94; 95% CI 0·88, 0·99). This association was confirmed for total cardiovascular as well as myocardial infarction (MI) incidence and mortality, but not for stroke. Score 3 was slightly more associated with the same outcomes. All associations were also resistant to adjustment for covariates related to potential CVD pathways, such as blood lipids, blood pressure and weight change after 11 years of follow-up. In a Danish cohort, the MDS was inversely associated with total mortality and with cardiovascular and MI incidence and mortality, but not with stroke incidence or mortality.
  •  
42.
  • Tognon, Gianluca, 1976, et al. (författare)
  • The Mediterranean diet score and mortality are inversely associated in adults living in the subarctic region.
  • 2012
  • Ingår i: The Journal of nutrition. - : Elsevier BV. - 1541-6100 .- 0022-3166. ; 142:8, s. 1547-53
  • Tidskriftsartikel (refereegranskat)abstract
    • The Mediterranean diet has been widely promoted and may be associated with chronic disease prevention and a better overall health status. The aim of this study was to evaluate whether the Mediterranean diet score inversely predicted total or cause-specific mortality in a prospective population study in Northern Sweden (Västerbotten Intervention Program). The analyses were performed in 77,151 participants (whose diet was measured by means of a validated FFQ) by Cox proportional hazard models adjusted for several potential confounders. The Mediterranean diet score was inversely associated with all-cause mortality in men [HR = 0.96 (95% CI = 0.93, 0.99)] and women [HR = 0.95 (95% CI = 0.91, 0.99)], although not in obese men. In men, but not in women, the score was inversely associated with total cancer mortality [HR = 0.92 (95% CI = 0.87, 0.98)], particularly for pancreas cancer [HR = 0.82 (95% CI = 0.68, 0.99)]. Cardiovascular mortality was inversely associated with diet only in women [HR = 0.90 (95% CI = 0.82, 0.99)]. Except for alcohol [HR = 0.83 (95% CI = 0.76, 0.90)] and fruit intake [HR = 0.90 (95% CI = 0.83, 0.98)], no food item of the Mediterranean diet score independently predicted mortality. Higher scores were associated with increasing age, education, and physical activity. Moreover, healthful dietary and lifestyle-related factors additively decreased the mortality likelihood. Even in a subarctic region, increasing Mediterranean diet scores were associated with a longer life, although the protective effect of diet was of small magnitude compared with other healthful dietary and lifestyle-related factors examined.
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