Targeting Sphingosine Kinase 1 in Carcinoma Cells Decreases Proliferation and Survival by Compromising PKC Activity and Cytokinesis

Sphingosine kinases (SK) catalyze the phosphorylation of proapoptotic sphingosine to the prosurvival factor sphingosine 1-phosphate (S1P), thereby promoting oncogenic processes. Breast (MDA-MB-231), lung (NCI-H358), and colon (HCT 116) carcinoma cells were transduced with shRNA to downregulate SK-1 expression or treated with a pharmacologic SK-1 inhibitor. The effects of SK-1 targeting were investigated by measuring the level of intracellular sphingosine, the activity of protein kinase C (PKC) and cell cycle regulators, and the mitotic index. Functional assays included measurement of cell proliferation, colony formation, apoptosis, and cell cycle analysis. Downregulation of SK-1 or its pharmacologic inhibition increased intracellular sphingosine and decreased PKC activity as shown by reduced phosphorylation of PKC substrates. In MDA-MB-231 cells this effect was most pronounced and reduced cell proliferation and colony formation, which could be mimicked using exogenous sphingosine or the PKC inhibitor RO 31-8220. SK-1 downregulation in MDA-MB-231 cells increased the number of cells with 4N and 8N DNA content, and similar effects were observed upon treatment with sphingosine or inhibitors of SK-1 or PKC. Examination of cell cycle regulators unveiled decreased cdc2 activity and expression of Chk1, which may compromise spindle checkpoint function and cytokinesis. Indeed, SK-1 kd cells entered mitosis but failed to divide, and in the presence of taxol also failed to sustain mitotic arrest, resulting in further increased endoreduplication and apoptosis. Our findings delineate an intriguing link between SK-1, PKC and components of the cell cycle machinery, which underlines the significance of SK-1 as a target for cancer therapy

Die Geschichte einer unbekannten dermatologischen Wachsgusssammlung der Universität „Iuliu Hatieganu“, Klausenburg, Rumänien

Among the dermatological wax collections across Europe, one of the latest created is the collection from Cluj-Napoca University, Romania. The initiator was Professor Coriolan Tataru and the moulage artist employed was Dr. Richard Hoffmann. Between the years 1923 and 1928, around 200 wax moulages were made, all realised after patients hospitalised in the clinic. The majority of cases represent the dermatological infectious pathology of that time: syphilis, cutaneous tuberculosis and mycetomas. Other interesting moulages represent genodermatoses, pelagra, different cutaneous cancers, and atypical aspects of common diseases like psoriasis and eczemas. The models depicting different stages of syphilis won the gold medal at the Ninth International Congress of Dermato-Venereology held in Budapest in 1935. We believe that the collection has a great value from a historical, artistic, didactic and scientific point of view, and it is organised as a museum within the Dermatology Clinic

Electroweak parameters of the z0 resonance and the standard model

Contains fulltext : 124399.pdf (publisher's version ) (Open Access

Wax Anatomical Models and Neuroscience: From Artistic Italian Creation to Therapeutic Approach

Wax modelling has been used since ancient times with its first application in art in the fifteenth century involving famous artists with knowledge of anatomy. It was only in the seventeenth century that coloured ceroplastic began to be used for teaching anatomy as valid alternative to dissected human bodies, including also neuropathological. The origin of this scientific approach was born in central Italy, in Florence and Bologna in the eighteenth century, and immediately spread to other Italian cities, and Europe, and throughout the rest of the world. Wax neuro-models were shown as artefacts and destined to train young doctors in anatomical knowledge. Nowadays, wax is often considered an old-fashioned art form but what is not well known is that wax has a useful therapeutic application in medicine, with a particular emphasis in neurosurgery