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- Bottone, Maria Grazia, et al.
(författare)
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Multiple effects of paclitaxel are modulated by a high c-myc amplification level.
- 2003
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Ingår i: Experimental cell research. - 0014-4827. ; 290:1, s. 49-59
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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)
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Unique features of the mode of action of ET-743.
- 2002
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Ingår i: The oncologist. - 1083-7159. ; 7:3, s. 210-6
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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)
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Effect of Aplidin in acute lymphoblastic leukaemia cells.
- 2003
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Ingår i: British journal of cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 89:4, s. 763-73
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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)
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Is "junk food" an "healthy concept"? From policy making back to science
- 2014
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Ingår i: British Food Journal. - 0007-070X. ; 116:8, s. 1222-1232
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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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| 9. |
- Finardi, C., et al.
(författare)
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"Is 'junk food' an 'healthy' concept?" the challenges of the current debate From policy making back to science
- 2014
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Ingår i: British Food Journal. - : Emerald. - 0007-070X. ; 116:8, s. 1222-1232
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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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| 10. |
- González-Gil, Esther María, et al.
(författare)
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Prospective associations between dietary patterns and high sensitivity C-reactive protein in European children: the IDEFICS study.
- 2018
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Ingår i: European journal of nutrition. - : Springer Science and Business Media LLC. - 1436-6215 .- 1436-6207. ; 57:4, s. 1397-1407
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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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