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Sökning: WFRF:(Wiren S)

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  • Olofsson Bagge, Roger, 1978, et al. (författare)
  • A phase Ib randomized multicenter trial of isolated hepatic perfusion in combination with ipilimumab and nivolumab for uveal melanoma
  • 2024
  • Ingår i: ESMO OPEN. - : Elsevier. - 2059-7029. ; 9:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Uveal melanoma (UM) is a rare malignancy where 50% of patients develop metastatic disease primarily affecting the liver. Approximately 40% of patients with metastatic UM respond to one-time isolated hepatic perfusion (IHP) with high -dose melphalan. This phase I trial investigates the safety and clinical ef fi cacy of IHP combined with ipilimumab (IPI) and nivolumab (NIVO). Patients and methods: Immunotherapy-na & iuml;ve patients were randomized in this phase I trial to receive either IHP followed by IPI 3 mg/kg and NIVO 1 mg/kg (IPI3/NIVO1) for four cycles (post -operative arm), or one cycle of preoperative IPI3/NIVO1, IHP and then three cycles of IPI3/NIVO1 (pre-post-operative arm), followed by maintenance therapy with NIVO 480 mg for 1 year. Results: Eighteen patients were enrolled and randomized. Three patients did not undergo IHP as planned. In total, 11/ 18 patients (6 in the post -operative arm and 5 in the pre-post-operative arm) did not complete the planned four cycles of IPI3/NIVO1. Toxicity to IHP was similar in both groups, but the number of immune-related adverse events (AEs) was higher in the pre-post-operative arm. Among assessable patients, overall response rate was 57% in the post -operative arm (4/7) and 22% in the pre-post-operative arm (2/9). Conclusions: Combination therapy with IHP and IPI3/NIVO1 was associated with severe AEs. The ef fi cacy of this combination is encouraging with high response rates. One cycle of preoperative IPI/NIVO before IHP did not show potential bene fi ts in terms of safety or ef fi cacy.
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  • Roguev, A., et al. (författare)
  • High-throughput genetic interaction mapping in the fission yeast Schizosaccharomyces pombe
  • 2007
  • Ingår i: Nature Methods. - : Springer Science and Business Media LLC. - 1548-7091 .- 1548-7105. ; 4:10, s. 861-866
  • Tidskriftsartikel (refereegranskat)abstract
    • Epistasis analysis, which reports on the extent to which the function of one gene depends on the presence of a second, is a powerful tool for studying the functional organization of the cell. Systematic genome-wide studies of epistasis, however, have been limited, with the majority of data being collected in the budding yeast, Saccharomyces cerevisiae. Here we present two 'pombe epistasis mapper' strategies, PEM-1 and PEM-2, which allow for high-throughput double mutant generation in the fission yeast, S. pombe. These approaches take advantage of a previously undescribed, recessive, cycloheximide-resistance mutation. Both systems can be used for genome-wide screens or for the generation of high-density, quantitative epistatic miniarray profiles (E-MAPs). Since S. cerevisiae and S. pombe are evolutionary distant, this methodology will provide insight into conserved biological pathways that are present in S. pombe, but not S. cerevisiae, and will enable a comprehensive analysis of the conservation of genetic interaction networks.
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