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- Girnita, L., et al.
(författare)
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Increased expression of insulin-like growth factor I receptor in malignant cells expressing aberrant p53 : Functional impact
- 2000
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Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 60:18, s. 5278-5283
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the functional impact of p53 on insulin-like growth factor I receptor (IGF-IR) expression in malignant cells. Using the BL-41tsp53-2 cell line, a transfectant carrying temperature-sensitive (ts) p53 and endogenous mutant p53 (codon 248), we demonstrated a drastic down-regulation of plasma membrane-bound IGF-IRs on induction of wild-type p53, However, a similar response was obtained by treatment of BL-41tsp53-2 cells expressing mutant ts p53 with a p53 antisense oligonucleotide. Thus, even if the negative effect of wild-type p53 predominates under a competitive condition, these data indicate that mutant p53 may be important for up-regulation of IGF-IR, To further elucidate this issue, three melanoma cell lines (BE, SK-MEL-5, and SK-MEL-28) that over expressed p53 were investigated. The BE cell line has a hot spot mutation (codon 248) and expresses only codon 248-mutant p53, SK-MEL-28 has a point mutation at codon 145. SK-MEL-5 cells did not exhibit any p53 mutations, but the absence of p21(Waf1) expression suggested functionally aberrant p53. Our data suggest that interaction with Mdm-2 may underlie p53 inactivation in these cells, Using p53 antisense oligonucleotides, we demonstrated a substantial down-regulation of cell surface expression of IGF-IR proteins in all melanoma cell lines after 24 h, This was paralleled by decreased tyrosine phosphorylation of IGF-IR and growth arrest, and, subsequently, massive cell death was observed (this was also seen in BL-41tsp53-2 cells with mutant conformation of ts p53). Taken together, our results suggest that up-regulation of IGF-IR as a result of expression of aberrant p53 may be important for the growth and survival of malignant cells.
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- Bennet, A. M., et al.
(författare)
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Association of TNF-α serum levels and TNFA promoter polymorohisms with risk of myocardial infarction
- 2006
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Ingår i: Atherosclerosis. - : Elsevier. - 0021-9150 .- 1879-1484. ; 187:2, s. 408-414
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Tidskriftsartikel (refereegranskat)abstract
- Elevated levels of tumor necrosis factor-alpha (TNF-α), and presence of polymorphisms of the TNFA gene have been implicated in cardiovascular disease pathogenesis. We explored the relationship between polymorphisms in the TNFA gene (−1031C/T, −863C/A −857T/C, −308G/A, −238G/A), protein levels of TNF-α and their association to myocardial infarction (MI) using a sample of 1213 post-MI patients and 1561 healthy controls. MI risk was higher among men with elevated TNF-α levels, with the highest compared to the lowest TNF-α quartile giving a 70% risk increase (OR [95% CI]: 1.7 [1.1; 2.6]). Obese subjects who also had elevated TNF-α levels were at even higher risk for MI (OR [95% CI]: 3.4 [2.1; 5.6]). Higher TNF-α levels were seen among smokers (but not among non-smokers) carrying the −857T allele. Furthermore, a rare haplotype occurred more frequently among the cases than the controls. Elevated TNF-α levels are associated with increased MI risk. Obese subjects with elevated TNF-a levels, and carriers of polymorphisms in or near TNFA are particularly susceptible to the hazards of smoking, results which may have implications for cardiovascular preventive measures.
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- Follin, P, et al.
(författare)
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Effective control measures limited measles outbreak after extensive nosocomial exposures in January-February 2008 in Gothenburg, Sweden.
- 2008
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Ingår i: Euro surveillance : bulletin européen sur les maladies transmissibles = European communicable disease bulletin. - 1560-7917. ; 13:30, s. 1-5
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Tidskriftsartikel (refereegranskat)abstract
- In January-February 2008, one imported case of measles initiated a series of exposures with around 380 nosocomial secondary contacts. Susceptible individuals were traced early and control measures were initiated that managed to limit the consequences considerably. Only four secondary cases were identified by the end of March. This minor outbreak illustrates the importance and efficiency of early control measures as well as the fact that the risk of measles outbreaks still exists in a country that has high measles, mumps, rubella vaccination coverage among children.
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- Reuterwall, C, et al.
(författare)
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Higher relative, but lower absolute risks of myocardial infarction in women than in men : analysis of some major risk factors in the SHEEP study. The SHEEP Study Group.
- 1999
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 246:2, s. 161-74
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Middle-aged men have often been the subjects of multifactorial studies of myocardial infarction (MI) risk factors. One major objective of the SHEEP study was to compare the effects of different MI risk factors in women and men. DESIGN: SHEEP (Stockholm Heart Epidemiology Program) is a population-based case-referent study of causes of MI (first event) in Swedish women and men aged 45-70 years. During the period 1992-94, 2246 cases of MI were identified; 34% of the cases were women and 27% of the cases were fatal. One referent per case was chosen randomly from the Stockholm County population after stratification for the case's sex and age. Logistic regression was used to estimate the relative risks associated with risk factors of primary interest (diabetes, hypercholesterolaemia, hypertriglyceridaemia, hypertension, overweight, physical inactivity, smoking and job strain). RESULTS: The relative risk estimates ranged from 1.5 to 4.4 in women and from 1.3 to 2.9 in men (results for nonfatal cases and their referents). None of the 95% confidence intervals included 1.0. The relative risks were higher in the women than in the men (101-180%). The absolute risks, however, were all lower in the women than in the men. Estimates of Rothman's synergy index for gender ranged from 1.0 (hypertension) to 1.8 (current smoking). CONCLUSIONS: The indications of some effect modification due to sex (stronger risks in men for certain exposures) invoke the question of possible mechanisms.
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- Xu, DW, et al.
(författare)
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Downregulation of telomerase reverse transcriptase mRNA expression by wild type p53 in human tumor cells
- 2000
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Ingår i: Oncogene. - 0950-9232 .- 1476-5594. ; 19:45, s. 5123-5133
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Tidskriftsartikel (refereegranskat)abstract
- The p53 tumor suppressor protein inhibits the formation of tumors through induction of cell cycle arrest and/or apoptosis, In the present study we demonstrated that p53 is also a powerful inhibitor of human telomerase reverse transcriptase (hTERT), a key component for telomerase, Activation of either exogenous temperature-sensitive (ts) p53 in BL41 Burkitt lymphoma cells or endogenous wild type (wt) p53 at a physiological level in MCF-7 breast carcinoma cells triggered a rapid downregulation of hTERT mRNA expression, independently of the induction of the p53 target gene p21, Co-transfection of an hTERT promoter construct with wt p53 but not mutant p53 in HeLa cells inhibited the hTERT promoter activity. Furthermore, the activation of the hTERT promoter in Drosophila Schneider SL2 cells was completely dependent on the ectopic expression of Sp1 and was abrogated by wt p53, Finally, wt p53 inhibited Sp1 binding to the hTERT proximal promoter by forming a p53-Sp1 complex. Since activation of telomerase, widely observed in human tumor cell lines and primary tumors, is a critical step in tumorigenesis, wt p53-triggered inhibition of hTERT/telomerase expression may reflect yet another mechanism of p53-mediated tumor suppression. Our findings provide new insights into both the biological function of p53 and the regulation of hTERT/telomerase expression.
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