The results confirm a protective role of preformed n-3 LCPs in the development of atopic disease. Moreover, this is the first study in humans confirming results from animal studies of protective effects of ruminant fatty acids against the development of atopic manifestations.
The inhibitor of apoptosis protein (IAP) survivin is overexpressed in many tumors but is absent in most normal adult tissues. We report high levels of survivin expression in small cell lung cancer (SCLC), and describe the role of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway in survivin upregulation. Moreover, the cytoprotective function of survivin in response to the anti-cancer agent cisplatin (CDDP) was investigated. Negative modulation of PI3K/ Akt using pharmacological inhibitors or dominant negative Akt (DN-Akt) decreased Akt kinase activity and resulted in decreased survivin expression and phosphorylation on Thr34, whereas transfection of constitutively active Akt (CA-Akt) increased survivin expression and phosphorylation. Interestingly, we found that treatment of SCLC cells with CDDP further increased survivin expression in a cell cycle independent manner by activation of Akt. CA-Akt or lentiviral survivin also inhibited apoptosis induced by CDDP, whereas DN-Akt or survivin-specific RNA interference sensitized cells to CDDP. We identified survivin as an anti-apoptotic protein in SCLC cells that is regulated by Akt, and demonstrate that treatment with the DNA damaging agent CDDP activates the PI3K/Akt/survivin pathway that in part protects cells from drug-induced apoptosis. ' 2005 Wiley-Liss, Inc.
ReviewsThis document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.Bryophyllum (see below) [4]. While these reviews describe various compounds and bioactivities, none of them addresses the pharmacological and clinical data that support the therapeutic use of Bryophyllum preparations in European countries. The present review focuses on B. pinnatum, but the few data available on Bryophyllum daigremontianum, Bryophyllum delagoense, and the hybrid Bryophyllum daigremontianum x tubiflorum have also been included. The German homeopathic pharmacopeia (HAB) 2014 [5] lists the two species B. pinnatum and B. daigremontianum as officinal in its monography "Bryophyllum Rh", and both have been used in AM. B. delagoense was introduced in the 1980s as an anthroposophic medicinal product in Germany, primarily for sedative purposes (Personal communication, Dr. med. Siegward-M. Elsas, see Acknowledgments).
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Overexpression of the anti-apoptotic proteins bcl-2 and bcl-xL is implicated in breast cancer development, tumor progression and drug resistance. Here we describe the use of the bcl-2/bcl-xL bispecific antisense oligonucleotide 4625 to sensitize breast carcinoma cells to anti-cancer drugs routinely used in breast cancer therapy. MCF7 cells were treated with oligonucleotide 4625, doxorubicin, paclitaxel or cyclophosphamide alone, or with combinations of oligonucleotide and the anti-cancer drugs. As measured in cell viability assays, treatment with the various combinations reduced the number of viable MCF7 cells more effectively than treatment with the single drugs alone. Treatment with a sequence control oligonucleotide did not affect cell viability. All combination treatments induced apoptosis as demonstrated by the appearance of massive nuclear condensation in a high proportion of the cells. To further characterize the interaction between 4625 and doxorubicin, paclitaxel or cyclophosphamide, the median-effect method was used. In MCF7 cells all combinations resulted in potent synergistic effects over a broad range of toxicity with combination indices ranging from 0.8 to 0.1. Similarly, strong synergistic interactions between oligonucleotide 4625 and the anti-cancer drugs were also observed in cultures of the breast carcinoma cell line MDA-MB-231. Our data suggest the use of 4625 as a potent adjuvant in breast cancer chemotherapy.
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