Doxycycline has anti-tumour effects in a range of tumour systems. The aims of this study were to define the role mitochondria play in this process and examine the potential of doxycycline in combination with gemcitabine. We studied the adenocarcinoma cell line A549, its mitochondrial DNA-less derivative A549 ρ° and cultured fibroblasts. Treatment with doxycycline for 5 days resulted in a decrease of mitochondrial-encoded proteins, respiration and membrane potential, and an increase of reactive oxygen species in A549 cells and fibroblasts, but fibroblasts were less affected. Doxycycline slowed proliferation of A549 cells by 35%. Cellular ATP levels did not change. Doxycycline alone had no effect on apoptosis; however, in combination with gemcitabine given during the last 2 days of treatment, doxycycline increased caspase 9 and 3/7 activities, resulting in a further decrease of surviving A549 cells by 59% and of fibroblasts by 24% compared to gemcitabine treatment alone. A549 ρ° cells were not affected by doxycycline. Key effects of doxycycline observed in A549 cells, such as the decrease of mitochondrial-encoded proteins and surviving cells were also seen in the cancer cell lines COLO357 and HT29. Our results suggest that doxycycline suppresses cancer cell proliferation and primes cells for apoptosis by gemcitabine.

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Measurement of IgE antibodies against purified grass pollen allergens (Lol p 1, 2, 3 and 5) during immunotherapy van Ree, R.; Leeuwen, W.A.; Dieges, P.H.; van Wijk, R.G.; de Jong, N.; Brewczyski, P.Z.; Kroon, A.M.; Schilte, P.P.M.; Tan, K.Y.; Simon-Licht, I.F.; Roberts, A.M.; Stapel, S.; Aalberse, R.C. Published in:Clinical and Experimental Allergy DOI:10.1046/j. 1365-2222.1997.d01-416.x Link to publication Citation for published version (APA): van Ree, R., Leeuwen, W. A., Dieges, P. H., van Wijk, R. G., de Jong, N., Brewczyski, P. Z., ... Aalberse, R. C. (1997). Measurement of IgE antibodies against purified grass pollen allergens (Lol p 1, 2, 3 and 5) during immunotherapy. Clinical and Experimental Allergy, 27, 68-74. https://doi.org/10.1046/j. 1365-2222.1997.d01-416.x General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulationsIf you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: http://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. Download date: 22 Mar 2019Cliniecd and Experimenhd Allergy. 1997, Volume 27, pages 68-74 Measurement of IgE antibodies against purified grass pollen allergens (Lol p 1, 2, 3 and 5) during immunotherapy R. VAN SummaryBackground IgE titres tend to rise early after the start of immunotherapy, followed by a decline to pre-immunotherapy levels or lower. Objectives We were interested to ktiow whether the early increase in IgE antibodies includes new specificities of IgE, and whether these responses persist. Methods Sera of 64 patients undergoing grass pollen immunotherapy were tested for IgE against four purified grass pollen allergens: Lol p 1. 2, 3, and 5. At least two serum samples were taken, one before the start of therapy and one between 5 and 18 months after the first immunization (mean: 10 months). Results The mean IgE responses to Lol p 1,2 and 3 showed a moderate but not significant increase. In contrast, the mean IgE response to Lol p 5 showed a significant decrease of >30%. IgE against total Lolium perenne pollen extract moderately increased (>20%), showing that a RAST for total pollen is not always indicative for the development of IgE against its major allergens. For >A{)% of the patients it was found that IgE against one or more of the four allergens increased, while IgE against the remaining allergen(s) decreased. Eor 10 sera the ratio of IgE titres against at least two allergens changed by at least a factor of 5. The changes ...