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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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