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- Iacopetta, B, et al.
(författare)
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Functional categories of TP53 mutation in colorectal cancer: results of an International Collaborative Study.
- 2006
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Ingår i: Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. - : Elsevier BV. - 0923-7534. ; 17:5, s. 842-7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Loss of TP53 function through gene mutation is a critical event in the development and progression of many tumour types including colorectal cancer (CRC). In vitro studies have found considerable heterogeneity amongst different TP53 mutants in terms of their transactivating abilities. The aim of this work was to evaluate whether TP53 mutations classified as functionally inactive (< or=20% of wildtype transactivation ability) had different prognostic and predictive values in CRC compared with mutations that retained significant activity. MATERIALS AND METHODS: TP53 mutations within a large, international database of CRC (n = 3583) were classified according to functional status for transactivation. RESULTS: Inactive TP53 mutations were found in 29% of all CRCs and were more frequent in rectal (32%) than proximal colon (22%) tumours (P < 0.001). Higher frequencies of inactive TP53 mutations were also seen in advanced stage tumours (P = 0.0003) and in tumours with the poor prognostic features of vascular (P = 0.006) and lymphatic invasion (P = 0.002). Inactive TP53 mutations were associated with significantly worse outcome only in patients with Dukes' stage D tumours (RR = 1.71, 95%CI 1.25-2.33, P < 0.001). Patients with Dukes' C stage tumours appeared to gain a survival benefit from 5-fluorouracil-based chemotherapy regardless of TP53 functional status for transactivation ability. CONCLUSIONS: Mutations that inactivate the transactivational ability of TP53 are more frequent in advanced CRC and are associated with worse prognosis in this stage of disease.
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- Robson, W. L. M., et al.
(författare)
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The comparative safety of oral versus intranasal desmopressin for the treatment of children with nocturnal enuresis
- 2007
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Ingår i: Journal of Urology. - : Ovid Technologies (Wolters Kluwer Health). - 1527-3792 .- 0022-5347. ; 178:1, s. 24-30
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Forskningsöversikt (refereegranskat)abstract
- Purpose: Desmopressin is a well established and effective therapy for nocturnal enuresis. Water intoxication leading to hyponatremia is an infrequent but serious adverse event associated with desmopressin. We assessed the safety of desmopressin in children 18 years or younger with nocturnal enuresis with a focus on the relative safety of the oral compared with the intranasal formulation. Materials and Methods: Published data (MEDLINE (R)) from December 1972 to August 2006 and post-marketing safety data from December 1972 to June 2005 were analyzed. Results: A total of 21 clinical trials on desmopressin use in children with nocturnal enuresis were identified. There were no reports of hyponatremia. A total of 21 publications were identified that included 48 case reports of hyponatremia in children with nocturnal enuresis. In all case reports patients were treated with intranasal desmopressin. Post-marketing safety data included 151 cases of hyponatremia in children with nocturnal enuresis, of whom 145 were treated with intranasal desmopressin and 6 were treated with the tablet formulation. Prodromal symptoms of hyponatremia were identified as headache, nausea and vomiting. Conclusions: Data suggest that there is a decreased risk of hyponatremia with oral desmopressin compared with intranasal desmopressin. Identifiable and preventable risk factors for hyponatremia are inappropriately high fluid intake, administration of a larger than recommended dose, young age (less than 6 years) and concomitant administration of another medication. When desmopressin is prescribed, patients should be instructed to avoid high fluid intake when the medication is ingested, not ingest a higher than recommended dose and promptly discontinue the medication and seek assessment if headache, nausea or vomiting develops.
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- Tolstoy, Päivi, et al.
(författare)
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Iridium-Catalyzed Asymmetric Hydrogenation yielding Chiral Diarylmethines with Weakly Coordinating or Noncoordinating Substituents
- 2009
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 131:25, s. 8855-8860
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Tidskriftsartikel (refereegranskat)abstract
- Diarylimethine-containing stereocenters are present in pharmaceuticals and natural products, making the synthetic methods that form these chiral centers are important in industry. We have applied iridium complexes with novel N,P-chelating ligands to the asymmetric hydrogenation of trisubstituted olefins, forming diarylmethine chiral centers in high conversions and excellent enantioselectivities (up to 99% ee) for a broad range of substrates. Our results support the hypothesis that steric hindrance in one specific area of the catalyst is playing a key role in stereoselection, as the hydrogenation of substrates differing little at the prochiral carbon occurred with high enantioselectivity. As a result, excellent stereodiscrimination was obtained even when the prochiral carbon bore, for example, phenyl and p-tolyl groups.
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