Arsenic trioxide down-regulates antiapoptotic genes and induces cell death in mycosis fungoides tumors in a mouse model.

BACKGROUND: Mycosis fungoides (MF) is the most frequent cutaneous T-cell lymphoma (CTCL). Arsenic trioxide (As(2)O(3)) has recently been shown to be effective against leukemias, so we studied whether As(2)O(3) induces apoptosis of CTCL cells in vitro. We further investigated if As(2)O(3) is effective in a MF mouse model. MATERIAL AND METHODS: Annexin V/7-amino-actinomycin-D stainings were carried out to investigate if As(2)O(3) induced apoptosis of CTCL cell lines. To study the underlying mechanisms, the effects of As(2)O(3) on various transcription factors and apoptosis regulating proteins were analyzed by western blots, electrophoretic mobility shift assays and transcription factor enzyme-linked immunosorbent assays. The ability of As(2)O(3) to induce tumor regression was investigated in a MF mouse model. RESULTS: As(2)O(3)-induced apoptosis was paralleled by a reduction of the DNA-binding activities of transcription factors of the NFkB and signal transducer and activator of transcription gene families and reduced expression of the antiapoptotic proteins bcl-1, bcl-xL and mcl-1. Local injections of 200 muM As(2)O(3) into tumors caused complete remissions in five of six mice and one partial remission. CONCLUSIONS: As(2)O(3) induced apoptosis of CTCL cells by the down-regulation of transcription factors that stimulate the expression of antiapoptotic genes. Local injection of As(2)O(3) into MF tumor-bearing mice resulted in tumor regression.

Antigen-pulsed dendritic cell approach to melanoma.

Dendritic cells (DCs) are potent antigen-presenting cells (1) with wide tissue distribution. They are classified based primarily on their localization: as Langerhans cells when present in the epidermis and as dermal DCs when found in the dermis. DCs exhibit several common features: an irregular shape with elongated dendritic processes, a distinctive cell-surface phenotype, low buoyant density, active motility, and the ability to stimulate vigorous proliferation of unprimed T-cells. DCs are able to ingest, process, and present antigen in the context of major histocompatibility complex (MHC) molecules. However, because of their high expression of MHC class I and II, as well as costimulatory molecules and adhesion molecules, DCs have the ability to induce primary T-cell-dependent immune responses in vivo and in vitro. This outstanding feature gives DCs a central role in controlling adaptive T-cell-based immunity.

Chondrocyte-biocompatibility of DegraPol-foam: in vitro evaluations.

Histological and biochemical investigations were carried out in order to evaluate the chondrocyte compatibility of a recently developed biodegradable polyesterurethane-foam (DegraPol-foam). Therefore, cell adhesion, cell growth, and the preservation of chondrocyte phenotype was measured in rat xyphoid chondrocytes seeded on DegraPol-foam. Chondrocytes, isolated from xyphoids of adult male rats, exhibited relatively high cell adhesion on DegraPol-foam (about 60% of that found on TCPS). Scanning electron microscopy (SEM) showed that chondrocytes grew on the surface and into the open cell pores of the foam. Morphologically, cells found on the surface of the foam exhibited a flat cell appearance and built a confluent cell multilayer. In contrast, the interior of the foam cells showed rounded morphology in cell aggregates and cell islets. In addition, chondrocytes proliferated on the DegraPol-foam (doubling-time of about 12.5 days) and preserved their phenotype for up to 14 days. Compared to freshly isolated chondrocytes, cells seeded on the foam produced high concentrations of collagen type II for up to 2 weeks: the ratio of type II/I collagen was 1.2-1.4 fold higher than the ratio found in freshly isolated cells. No significant difference was observed in chondroitin sulfate levels produced by freshly isolated cells and cells cultured on DegraPol-foam for up to 14 days. To sum up, our results indicate that DegraPol-foam is a compatible substrate for chondrocytes.

[Vaccination therapy of malignant melanoma]. / Vakzinationstherapie des malignen Melanoms.

There is no cure for advanced melanoma. Chemo- or chemo-immunotherapy may lead to tumor regression in a minority of patients. New perspectives for treatment derive from recent efforts to develop vaccination strategies for melanoma. Insights into the immunobiology of this disease combined with the characterization of tumor specific peptide epitopes as well as appreciation of the crucial role of dendritic cells for the induction of anti-tumor immunity are beginning to be translated into the every day clinical practice.