Chaetoglobosin A preferentially induces apoptosis in chronic lymphocytic leukemia cells by targeting the cytoskeleton.

Chronic lymphocytic leukemia (CLL) is an incurable malignancy of mature B cells. One of the major challenges in treatment of CLL is the achievement of a complete remission to prevent relapse of disease originating from cells within lymphoid tissues and subsequent chemoresistance. In search for novel drugs that target CLL cells in protective microenvironments, we performed a fungal extract screen using cocultures of primary CLL cells with bone marrow-derived stromal cells. A secondary metabolite produced by Penicillium aquamarinium was identified as Chaetoglobosin A (ChA), a member of the cytochalasan family that showed preferential induction of apoptosis in CLL cells, even under culture conditions that mimic lymphoid tissues. In vitro testing of 89 CLL cases revealed effective targeting of CLL cells by ChA, independent of bad prognosis characteristics, like 17p deletion or TP53 mutation. To provide insight into its mechanism of action, we showed that ChA targets filamentous actin in CLL cells and thereby induces cell-cycle arrest and inhibits membrane ruffling and cell migration. Our data further revealed that ChA prevents CLL cell activation and sensitizes them for treatment with PI3K and BTK inhibitors, suggesting this compound as a novel potential drug for CLL.

Otitis externa in the dog -- a clinical and microbiological study.

The effect on canine otitis externa of a topical preparation composed of Fucidin, Framycetin, Nystatin, and Prednisolone was evaluated in a clinical trial comprising 235 dog ears. Cases caused by parasites or foreign bodies and cases requiring systemic therapy were excluded. Swabs from these and an additional 434 affected ears were examined bacteriologically and the sensitivity to antibiotics of the bacteria isolated determined. The infection most frequently diagnosed was staphylococci plus yeasts (29 % of total material) followed by pure yeast-infections (19 %) and pure staphylococcus infections (16 %). Pseudomonas aeruginosa and/or Proteus mirabilis were found in 7 % of the ears, while no organisms could be isolated from 22 %. Sensitivity tests showed a satisfactory in vitro effect of Neomycin (Framycetin) on most of the bacteria commonly isolated, and a very good effect of Fucidin on the staphylococci. Approximately 91 % of the ears treated were clinically cured or improved very considerably; the relation between clinical response and type of infection is shown diagrammatically in Fig. 1. It was confirmed that infections with Ps. aeruginosa represent a special problem; the results of post-treatment sensitivity tests seem to suggest, however, that a longer or more intense course of treatment than the one used in the trial (two weeks) would provide the answer to this.