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- Bergmann, T K, et al.
(författare)
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Impact of CYP2C8*3 on paclitaxel clearance: a population pharmacokinetic and pharmacogenomic study in 93 patients with ovarian cancer
- 2011
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Ingår i: PHARMACOGENOMICS JOURNAL. - : Nature Publishing Group. - 1470-269X .- 1473-1150. ; 11:2, s. 113-120
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Tidskriftsartikel (refereegranskat)abstract
- The primary purpose of this study was to evaluate the effect of CYP2C8*3 and three genetic ABCB1 variants on the elimination of paclitaxel. We studied 93 Caucasian women with ovarian cancer treated with paclitaxel and carboplatin. Using sparse sampling and nonlinear mixed effects modeling, the individual clearance of unbound paclitaxel was estimated from total plasma paclitaxel and Cremophor EL. The geometric mean of clearance was 385 l h(-1) (range 176-726 l h(-1)). Carriers of CYP2C8*3 had 11% lower clearance than non-carriers, P = 0.03. This has not been shown before in similar studies; the explanation is probably the advantage of using both unbound paclitaxel clearance and a population of patients of same gender. No significant association was found for the ABCB1 variants C1236T, G2677T/A and C3435T. Secondarily, other candidate single-nucleotide polymorphisms were explored with possible associations found for CYP2C8*4 (P = 0.04) and ABCC1 g.7356253C andgt; G (P = 0.04).
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| 4. |
- Westin, U., et al.
(författare)
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The effect of immediate-hypersensitivity reactions on the level of SLPI, granulocyte elastase, α1-antitrypsin, and albumin in nasal secretions, by the method of unilateral antigen challenge
- 1999
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Ingår i: Allergy: European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538. ; 54:8, s. 857-864
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aim of this paper was to investigate the role of SLPI in patients with allergic rhinitis. From this point of view, we also examined leukocyte elastase, α1-antitrypsin, and albumin. SLPI is an inhibitor of serine proteases such as leukocyte elastase, cathepsin G, and mast-cell chymase. Since chymase is considered to participate in mast-cell degranulation and histamine release, SLPI might act as a regulator of allergic reactions. Recent interest has been focused on leukocytes and allergy. Since SLPI is a strong inhibitor of leukocyte elastase, we also focused on the function of elastase in allergic rhinitis. Methods: We used the method of nasal lavage after unilateral nasal antigen challenge in atopic and healthy subjects. The ELISA quantified SLPI and elastase. Albumin and α1-antitrypsin were quantified by electroimmunoassay. Gel filtration was used to separate native SLPI from its complex with elastase. Results: There was a higher level of SLPI in lavage fluid from healthy subjects than from atopic patients. SLPI was increased on the contralateral side in atopic subjects after allergen challenge. The absence of increase in SLPI on the challenged side may be attributed to the increase in elastase and its binding to SLPI, which might have an effect on the immunoreactivity and interfere with the ELISA. It may then be assumed that there is an augmentation of SLPI on the challenged side as well. No increase was seen in healthy subjects. There was a higher concentration of elastase, α1-antitrypsin, and albumin before antigen challenge in atopic patients outside the pollen season than in healthy subjects. As expected, an increase was also seen in the challenged side exclusively in atopic subjects. Conclusions: The lower concentration of SLPI in nasal lavage fluid among the atopic patients than the healthy subjects indicates damaged mucosa. Neural reflexes are involved in SLPI release since there was an increase even in the contralateral nostril. A higher level of elastase and albumin before allergen challenge suggests chronic inflammation in nasal mucosa outside the pollen season. Leukocyte recruitment takes place in response to IgE-mediated reactions, which are reflected in an increase in elastase in response to allergen challenge.
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