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- LoRusso, Patricia M, et al.
(författare)
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Improvements in quality of life and disease-related symptoms in phase I trials of the selective oral epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 in non-small cell lung cancer and other solid tumors
- 2003
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Ingår i: Clinical Cancer Research. - 1078-0432. ; 9:6, s. 2040-2048
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The feasibility and utility of assessing quality of life (QoL) and disease-related symptoms in patients with advanced cancer have been evaluated in two Phase I clinical trials of p.o. administered ZD1839 ('Iressa'), an epidermal growth factor receptor tyrosine kinase inhibitor, in patients with advanced cancer. EXPERIMENTAL DESIGN: Functional Assessment of Cancer Therapy (FACT) questionnaires, including disease-specific subscales for lung, head and neck, colorectal, prostate, and ovarian cancer, were completed by patients in two open-label, Phase I, escalating multiple-dose safety and tolerability trials. RESULTS: In 157 patients, 92% of whom had received prior therapy, compliance in returning FACT questionnaires was 87% (European/Australian trial) and 57% (United States trial). This did not appear to be influenced by dose level or tumor type. For patients with colorectal, prostate, or ovarian cancer, median QoL [FACT and Trial Outcome Index (TOI)] scores deteriorated over time. In contrast, for patients with non-small cell lung cancer (NSCLC) or head and neck cancer, median FACT and TOI scores did not deteriorate significantly, and in the United States trial, head and neck cancer scores improved significantly over time. In patients with NSCLC, symptom-related scores measured by the Lung Cancer Subscale of FACT-L appeared sensitive to clinical change. CONCLUSIONS: QoL (FACT-L) questionnaires were used successfully in the Phase I clinical trials of ZD1839. They appeared to be a sensitive tool to monitor clinical changes for the five tumor types in these trials and showed that ZD1839 has the potential to improve patients' QoL.
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| 2. |
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| 3. |
- Björk, Anne, et al.
(författare)
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Measurements of ECP in serum and the impact of plasma coagulation
- 2000
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995. ; 55:5, s. 442-448
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Tidskriftsartikel (refereegranskat)abstract
- Serum measurement of ECP (eosinophil cationic protein) is used as an indication of eosinophil activation in diseases such as asthma. The levels are dependent on sample handling, since a certain amount of ECP is released during storage. The mechanisms that induce this in vitro release are not known, but are supposed to be related to the coagulation process. The aim of this study was to investigate this further. ECP was measured in EDTA plasma and serum at 22 and 37°C from healthy individuals and patients with asthma and allergy. The serum levels of ECP increased with temperature. Recalcification of citrated plasma in the presence of granulocytes with increasing concentrations of Ca2+ showed a dissociation between the levels of ECP and the occurrence of coagulation. Further experiments indicated that plasma coagulation is not of any importance for the degranulation of eosinophils, nor did the addition of platelets or mononuclear cells affect the ECP levels. Incubations of granulocytes with fresh or frozen plasma and Ca2+suggested the existence of a freezing labile factor in plasma, necessary for the degranulation of healthy eosinophils, but not for allergic/asthmatic eosinophils. Further experiments with pure eosinophils indicated the existence of factors in serum and plasma which facilitate ECP secretion of an active, temperature-dependent nature. We conclude that the raised ECP levels in serum, as compared to EDTA plasma, are unrelated to the coagulation process, but are due to the continuous secretion ex vivo of ECP from active eosinophils. This process is time and temperature dependent and may be facilitated by eosinophil-activating components in the extracellular environment.
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| 5. |
- Karlsson, Anne-Li, et al.
(författare)
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Bet v 1 homologues in strawberry identified as IgE-binding proteins and presumptive allergens
- 2004
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Ingår i: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; 59:12, s. 1277-1284
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Tidskriftsartikel (refereegranskat)abstract
- Background: No strawberry allergen has so far been identified and characterized. Methods: Serum samples were collected from patients with a suggestive case history of adverse reactions to strawberry and other fruits. Extracts from fresh and frozen strawberries were analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), Western blotting and mass spectrometry. Patient blood samples were analysed for inhibition of IgE binding and basophil degranulation. Results: Several IgE-binding proteins could be detected. In more than half of the patient sera, a 20/18-kDa doublet band was observed in Western blotting. These two bands were excised and analysed by mass spectrometry showing the presence of proteins belonging to the Bet v 1 family of allergens. Inhibition of the IgE binding to the 20/18-kDa doublet was obtained by addition of two recombinantly expressed allergens belonging to the Bet v 1 family (Bet v 1 and Mal d 1) and strawberry protein extract. In a cell-based assay of patient blood samples, basophil degranulation could be induced by strawberry protein extract and by Bet v 1 and Mal d 1. Conclusions: We conclude that strawberry homologues to Bet v 1 may be allergens of importance for adverse reactions to strawberry.
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