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1.
  • Jones, Robert P., et al. (author)
  • Patterns of Recurrence After Resection of Pancreatic Ductal Adenocarcinoma : A Secondary Analysis of the ESPAC-4 Randomized Adjuvant Chemotherapy Trial
  • 2019
  • In: JAMA Surgery. - : AMER MEDICAL ASSOC. - 2168-6254 .- 2168-6262. ; 154:11, s. 1038-1048
  • Journal article (peer-reviewed)abstract
    • Importance: The patterns of disease recurrence after resection of pancreatic ductal adenocarcinoma with adjuvant chemotherapy remain unclear.Objective: To define patterns of recurrence after adjuvant chemotherapy and the association with survival.Design, Setting, and Participants: Prospectively collected data from the phase 3 European Study Group for Pancreatic Cancer 4 adjuvant clinical trial, an international multicenter study. The study included 730 patients who had resection and adjuvant chemotherapy for pancreatic cancer. Data were analyzed between July 2017 and May 2019.Interventions: Randomization to adjuvant gemcitabine or gemcitabine plus capecitabine.Main Outcomes and Measures: Overall survival, recurrence, and sites of recurrence.Results: Of the 730 patients, median age was 65 years (range 37-81 years), 414 were men (57%), and 316 were women (43%). The median follow-up time from randomization was 43.2 months (95% CI, 39.7-45.5 months), with overall survival from time of surgery of 27.9 months (95% CI, 24.8-29.9 months) with gemcitabine and 30.2 months (95% CI, 25.8-33.5 months) with the combination (HR, 0.81; 95% CI, 0.68-0.98; P=.03). The 5-year survival estimates were 17.1% (95% CI, 11.6%-23.5%) and 28.0% (22.0%-34.3%), respectively. Recurrence occurred in 479 patients (65.6%); another 78 patients (10.7%) died without recurrence. Local recurrence occurred at a median of 11.63 months (95% CI, 10.05-12.19 months), significantly different from those with distant recurrence with a median of 9.49 months (95% CI, 8.44-10.71 months) (HR, 1.21; 95% CI, 1.01-1.45; P=.04). Following recurrence, the median survival was 9.36 months (95% CI, 8.08-10.48 months) for local recurrence and 8.94 months (95% CI, 7.82-11.17 months) with distant recurrence (HR, 0.89; 95% CI, 0.73-1.09; P=.27). The median overall survival of patients with distant-only recurrence (23.03 months; 95% CI, 19.55-25.85 months) or local with distant recurrence (23.82 months; 95% CI, 17.48-28.32 months) was not significantly different from those with only local recurrence (24.83 months; 95% CI, 22.96-27.63 months) (P=.85 and P=.35, respectively). Gemcitabine plus capecitabine had a 21% reduction of death following recurrence compared with monotherapy (HR, 0.79; 95% CI, 0.64-0.98; P=.03).Conclusions and Relevance: There were no significant differences between the time to recurrence and subsequent and overall survival between local and distant recurrence. Pancreatic cancer behaves as a systemic disease requiring effective systemic therapy after resection.Trial Registration: ClinicalTrials.gov identifier: NCT00058201, EudraCT 2007-004299-38, and ISRCTN 96397434. This secondary analysis of a randomized clinical trial investigates patterns of recurrence after adjuvant chemotherapy in pancreatic cancer and the association with survival.
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  • Piwowar, Alan M., et al. (author)
  • Investigating the effect of temperature on depth profiles of biological material using ToF‐SIMS
  • 2011
  • In: Surface and Interface Analysis. - 1096-9918 .- 0142-2421. ; 43:1-2, s. 207-210
  • Journal article (peer-reviewed)abstract
    • In this study we examine the depth profiles of two bio-materials, an amino acid (arginine) and a polypeptide (Gly-Gly-Tyr-Arg), to observe the effects of temperature on sample analysis with time of flight secondary ion mass spectrometry (ToF-SIMS). The samples were prepared as dried droplet films on silicon and were analyzed at room temperature (300 K) and at cryogenic temperatures (100 K). Under cryogenic analysis conditions, molecular ion yields at the steady state increased by factors of 1.8 and 5 for arginine and the tetrapeptide respectively compared to analysis at room temperature. Increases are also observed in arginine dimer and trimer ion formation by factors of 6 and 5 respectively, while the lower mass fragment ions investigated did not change in intensity by more than 30%. Further analysis of the results show that the decrease in the steady state ion yield with primary ion fluence at 300 K is reduced when analyzed at 100 K, indicating a decrease in chemical damage. These results suggest that analysis under cryogenic conditions provides several benefits for the analysis of biological compounds and hence for 3D molecular imaging of cells and tissue.
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5.
  • Piwowar, Alan M., et al. (author)
  • Top-down approach to studying biological components using ToF-SIMS
  • 2011
  • In: Surface and Interface Analysis. - 1096-9918 .- 0142-2421. ; 43:1-2, s. 265-268
  • Journal article (peer-reviewed)abstract
    • We present in this article a novel approach to identifying subcellular components from spectral images collected with ToF-SIMS. The method utilizes a separation technique to isolate and enrich cellular fractions which are then examined with ToF-SIMS to identify peak or peak ratio markers to assign reference spectra. The ultimate aim of the project is to utilize these reference spectra to identify cellular components from spectral images. We present data from three such extracts (nuclei, cytosol and membrane-bound organelles) which confirms that characteristic spectral differences do exist between these systems. These results indicate that such a ‘top-down’ approach to subcellular analysis can aid cellular imaging with ToF-SIMS.
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