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- Finglas, Paul M, et al.
(författare)
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Use of an oral/intravenous dual-label stable-isotope protocol to determine folic acid bioavailability from fortified cereal grain foods in women.
- 2002
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Ingår i: Journal of Nutrition. - 0022-3166 .- 1541-6100. ; 132:5
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Tidskriftsartikel (refereegranskat)abstract
- Folic acid fortification, mandatory in the United States, is currently being considered by the UK. The hypothesis that the matrix of some cereal-product vehicles may result in low fortificant bioavailability was tested using a dual oral/intravenous (i.v.) isotopic-label approach, which was evaluated concurrently. Fifteen women received 225 microg oral folate (capsules, fortified white bread and fortified branflakes), mainly as folic acid labeled with (13)C on 6 carbons of the benzoyl ring ((13)C(6)-PteGlu), followed by i.v. injection of 100 microg folic acid labeled with (2)H on 4 hydrogens of the glutamic acid group ((2)H(4)-PteGlu). The urinary excretion ratio (UER) in intact folate of the percentage of labeled oral dose excreted divided by the percentage of i.v. dose excreted was used as the primary index of absorption. The geometric mean (95% confidence interval) UER for folic acid capsules was 3.68 (1.90, 7.14) at 24 h and 2.18 (1.24, 3.83) at 48 h. Because these were significantly in excess of 1.0, indicative of 100% absorption of the oral dose, it was concluded that oral and i.v. labeled folic acid are handled differently by the body and that "absolute" absorption cannot be calculated. Compared with the 48-h UER for folic acid capsules, the "relative" 48-h UER for white bread and branflakes was 0.71 and 0.37, respectively, indicating that some cereal-based vehicles may inhibit absorption of fortificant. However, even the validity of this "relative" approach is questioned.
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| 2. |
- Heikkinen, Tuomas, et al.
(författare)
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Variants on the promoter region of PTEN affect breast cancer progression and patient survival
- 2011
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Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 13:6, s. R130-
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUTION:The PTEN gene, a regulator of the phosphatidylinositol-3-kinase (PI3K)/Akt oncogenic pathway, is mutated in various cancers and its expression has been associated with tumor progression in a dose-dependent fashion. We investigated the effect of germline variation in the promoter region of the PTEN gene on clinical characteristics and survival in breast cancer.METHODS:We screened the promoter region of the PTEN gene for germline variation in 330 familial breast cancer cases and further determined the genotypes of three detected PTEN promoter polymorphisms -903GA, -975GC, and -1026CA in a total of 2,412 breast cancer patients to evaluate the effects of the variants on tumor characteristics and disease outcome. We compared the gene expression profiles in breast cancers of 10 variant carriers and 10 matched non-carriers and performed further survival analyses based on the differentially expressed genes.RESULTS: All three promoter variants associated with worse prognosis. The Cox's regression hazard ratio for 10-year breast cancer specific survival in multivariate analysis was 2.01 (95% CI 1.17 to 3.46) P = 0.0119, and for 5-year breast cancer death or distant metastasis free survival 1.79 (95% CI 1.03 to 3.11) P = 0.0381 for the variant carriers, indicating PTEN promoter variants as an independent prognostic factor. The breast tumors from the promoter variant carriers exhibited a similar gene expression signature of 160 differentially expressed genes compared to matched non-carrier tumors. The signature further stratified patients into two groups with different recurrence free survival in independent breast cancer gene expression data sets.CONCLUSIONS:Inherited variation in the PTEN promoter region affects the tumor progression and gene expression profile in breast cancer. Further studies are warranted to establish PTEN promoter variants as clinical markers for prognosis in breast cancer.
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| 3. |
- Maunder, Peter, et al.
(författare)
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The synthesis of folic acid, multiply labelled with stable isotopes, for bio-availability studies in human nutrition
- 1999
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Ingår i: Journal of the Chemical Society-Perkin Transactions 1. - : Royal Society of Chemistry (RSC). - 0300-922X .- 1364-5463. ; :10, s. 1311-1323
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Tidskriftsartikel (refereegranskat)abstract
- Two different methods for the synthesis of folic acid, which are suitable for the incorporation of compounds multiply labelled with stable isotopes, are described. The first method is based on the use of a novel reductive amination to link 2-acetylamino-4-hydroxy-6-formylpteridine with p-aminobenzoyl-L-glutamic acid. The second method is based on the penultimate formation of an amide bond between N-2-acetyl-N-10-trifluoroacetylpteroic acid and dimethyl L-glutamate. Both methods have been used to transform [C-13(6)]aniline into folic acid, labelled with [C-13(6)] in the p-aminobenzoate moiety, and [3,3,4,4-H-2(4)]-L-glutamic acid into folic acid, labelled with [H-2(4)] in the glutamate moiety. Doubly labelled [C-13(6), H-2(4)]-p-aminobenzoyl-L-glutamate has also been prepared by the former method.
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