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Berlin, Germany

Harnack U.,Charite - Medical University of Berlin | Eckert K.,epo GmbH | Pecher G.,Charite - Medical University of Berlin
Anticancer Research | Year: 2011

Background: Beta-(1-3),(1-6)-D-glucans demonstrate antitumor effects in vivo due to the activation of innate immune cells. Cyclophosphamide (CY) enhances natural or therapeutically induced antitumor immune responses by reducing the number and activity of regulatory T (Treg) cells. Materials and Methods: We tested whether oral administration of soluble beta-glucan augmented the inhibitory effect of intraperitoneally injected low-dose CY (30 mg/kg) on subcutaneously growing A20-lymphoma in Balb/c-mice. Results: Administration of CY one week after tumor inoculation significantly diminished tumor growth (p=0.009) and the absolute number of Treg cells in the peripheral blood compared with phosphate buffered saline-treated mice (p=0.036). Treatment of CY pre-conditioned lymphoma-bearing mice with daily beta-glucan (400 μg/mouse) between day 9 and day 13 after tumor injection significantly delayed onset of tumor growth, compared to mice which received only CY (p=0.01). Conclusion: Beta-(1-3),(1-6)-D-glucan could be useful in the treatment of lymphoma after low-dose chemotherapy with CY.

Delebinski C.I.,Charite - Medical University of Berlin | Twardziok M.,Charite - Medical University of Berlin | Kleinsimon S.,Charite - Medical University of Berlin | Hoff F.,University of Marburg | And 5 more authors.
PLoS ONE | Year: 2015

Aqueous Viscum album L. extracts are widely used in complementary cancer medicine. Hydrophobic triterpene acids also possess anti-cancer properties, but due to their low solubility they do not occur in significant amounts in aqueous extracts. Using cyclodextrins we solubilised mistletoe triterpenes (mainly oleanolic acid) and investigated the effect of a mistletoe whole plant extract on human acute myeloid leukaemia cells in vitro, ex vivo and in vivo. Single Viscum album L. extracts containing only solubilised triterpene acids (TT) or lectins (viscum) inhibited cell proliferation and induced apoptosis in a dose-dependent manner in vitro and ex vivo. The combination of viscum and TT extracts (viscumTT) enhanced the induction of apoptosis synergistically. The experiments demonstrated that all three extracts are able to induce apoptosis via caspase-8 and -9 dependent pathways with downregulation of members of the inhibitor of apoptosis and Bcl-2 families of proteins. Finally, the acute myeloid leukaemia mouse model experiment confirmed the therapeutic effectiveness of viscumTT-treatment resulting in significant tumour weight reduction, comparable to the effect in cytarabine-treated mice. These results suggest that the combination viscumTT may have a potential therapeutic value for the treatment AML. © 2015 Delebinski et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Busia L.,Bayer AG | Busia L.,Free University of Berlin | Faus H.,Bayer AG | Hoffmann J.,Bayer AG | And 2 more authors.
Molecular and Cellular Endocrinology | Year: 2011

The ovarian steroid hormone progesterone is essential for normal mammary gland physiology but may also play a role in breast cancer. Highly potent and selective antiprogestins may therefore represent a new treatment option for this disease. Here we studied the effects of the new antiprogestin Lonaprisan on the T47D breast cancer cell line. Strong inhibition of cell proliferation and arrest in the G0/G1 phase were observed, as well as induction of a senescence-like phenotype. This was accompanied by p21 induction through direct binding of Lonaprisan-bound progesterone receptor (PR) to the promoter. Reduction of p21 levels blunted the antiproliferative effects of Lonaprisan. Mutation analysis showed that intact PR DNA-binding properties were needed for p21 induction. Phosphorylation of PR Ser345 was stimulated by Lonaprisan, but this post-translational modification was not required for p21 promoter activation, nor was the interaction with c-Src needed. These results support the rationale for using antiprogestins in breast cancer treatment and warrant further studies to better understand their mode of action. © 2010 Elsevier Ireland Ltd.

Harnack U.,Charite - Medical University of Berlin | Eckert K.,epo GmbH | Pecher G.,Charite - Medical University of Berlin
In Vivo | Year: 2011

Background: Therapeutic options for the treatment of malignant ascites are limited and could be broadened by immune-stimulatory drugs. Materials and Methods: Soluble β-(1-3),(1-6)-D-glucan from Saccharomyces cerevisiae was administered i.p. into DBA/2-mice bearing the P388 lymphoma either freshly inoculated or as an established ascites-tumor. Its effect on survival, ascites volume and production of cytokines was examined. Results: The early, but not the later, administration of β-glucan showed a tendency to induce interleukin (IL)-12 in the ascites, whereas both treatment schedules demonstrated a clear tendency to reduce production of interferon-γ in the abdominal fluid and had no notable impact on the level of tumor necrosis factor-α. Treatment with β-glucan at either time-point showed no effect on the ascites volume and mean survival time. Conclusion: β-(1-3), (1-6)-D-Glucan shows weak and differential modulation of immune-stimulatory and pro-inflammatory cytokines in tumor ascites dependent on the stage of tumor growth without affecting survival of the mice.

Wulf-Goldenberg A.,epo GmbH | Keil M.,Max Delbruck Center for Molecular Medicine | Keil M.,Charite - Medical University of Berlin | Fichtner I.,Max Delbruck Center for Molecular Medicine | Eckert K.,Max Delbruck Center for Molecular Medicine
Tissue and Cell | Year: 2012

In vivo studies concerning the function of human hematopoietic stem cells (HSC) are limited by relatively low levels of engraftment and the failure of the engrafted HSC preparations to differentiate into functional immune cells after systemic application. In the present paper we describe the effect of intrahepatically transplanted CD34 + cells from cord blood into the liver of newborn or adult NOD/SCID mice on organ engraftment and differentiation.Analyzing the short and long term time dependency of human cell recruitment into mouse organs after cell transplantation in the liver of newborn and adult NOD/SCID mice by RT-PCR and FACS analysis, a significantly high engraftment was found after transplantation into liver of newborn NOD/SCID mice compared to adult mice, with the highest level of 35% human cells in bone marrow and 4.9% human cells in spleen at day 70. These human cells showed CD19 B-cell, CD34 and CD38 hematopoietic and CD33 myeloid cell differentiation, but lacked any T-cell differentiation. HSC transplantation into liver of adult NOD/SCID mice resulted in minor recruitment of human cells from mouse liver to other mouse organs. The results indicate the usefulness of the intrahepatic application route into the liver of newborn NOD/SCID mice for the investigation of hematopoietic differentiation potential of CD34 + cord blood stem cell preparations. © 2011 Elsevier Ltd.

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