Glioblastoma multiforme: a multidisciplinary approach to overcome chemoresistance and find new therapeutic strategies

Objectives: Glioblastoma multiforme is the most frequent malignant brain tumor. Patients die within 15 months after diagnosis. The failure of current therapies is ascribed to a subpopulation of cells with stem-like properties, called glioma stem cells (GSCs). The aim of this study is to develop new effective therapies. Moreover, we want to better characterize the orthotopic xenograft model established by GSCs injection into NOD/SCID mice. Materials and methods: We tested Temolomide and Valproic acid treatments, alone and in combination, on seven GSC lines by MTT assay and we sequenced p53. Moreover, we characterized our xenograft model investigating the expression of stemness and differentiation markers by immunohistochemistry on FFPE tissues and by immunofluorescence on the correspondent cell line. Finally, we performed aCGH on the DNA extracted from the cell line and from FFPE tissues. Results: GSCs were resistant to Temozolomide and slightly sensitive to Valproic acid. The two drugs exerted a synergistic effect when combined performing a pre-conditioning with Valproic acid. Furthermore, several cell lines carry p53 mutations. IF and IHC showed a perfect correspondence for stemness markers expression, but discordant data for the others. aCGH analysis evidenced numerous alterations specific for the ex vivo sample, suggesting the presence of an in vivo clonal selection. Discussion: This work shows the importance of murine microenvironment in GSCs phenotype in vivo and suggests the possibility to use our combined treatment for therapeutic purposes. Conclusions: Orthotopic models from GSCs and in vitro grown cell lines represent good models for the development of GSC-targeted therapies

Influence of feed delivery frequency on behavioural activity of dairy cows in freestall barns

Research on feeding management in more competitive free-stall settings indicates that frequency of delivery of fresh feed stimulates feed bunk attendance and can affect other aspects of cows’ time budgets apart from feeding such as time spent standing vs. lying down. The objective of this study was to examine how the frequency of feed delivery affects the behavior in two farms, one with a conventional and one with automatic milking system (AMS). The feeding frequency was varied from two to three times per day in the conventional dairy farm; one to two times per day in the AMS farm. The experiment was carried out in two different seasons. All behaviours of the cows were monitored in continuous by video recording. As expected, behavioral indices have been significantly affected by environmental conditions both in conventional farm and AMS farm. The variation in the frequency of feed delivery seems to affect the cow behavioural activity only in a limited way and modify only slightly the daily averages of the time spent in different activities mainly increasing the time cows spend standing (+4- 5%)

Scientific achievements in the Clemente Susini’s wax anatomical models of the University of Cagliari

The waxes of Cagliari were manufactured between 1803-1805, and represent a work of the maturity of Clemente Susini (1754-1814) the chief modeller of La Specola. The dissections reproduced by Susini were carried out by Francesco Antonio Boi (Olzai,1767-Cagliari, 1865), from the University of Cagliari who had been sent on purpose to Florence by the Viceroy Carlo Felice of Savoy (1765-1831). The models which arrived in Cagliari in 1806 contained in 23 showcases, are attached to 23 wooden tables that bear the original tag with date and Susini’s signature. The latter is a distinctive character in that, of the over 2000 models accomplished under Susini’ guidance, only a few bear his signature. Moreover, they were made when Susini was eventually free from the influence of Felice Fontan. By order of Carlo Felice the models to be made for Cagliari, which consist of a special mix of waxes able to resist the hot climate of south Sardinia, had to be unique and, thus, at variance with those of La Specola, no copies of them are seen in other collections. On the other hand, possibly thanks to Francesco Antonio Boi, a few mistakes seen in the collections of Florence, Vienna, and Bologna, such as the presence of lymphatics in the human brain, are absent here. A distinctive character is the relevance given to visceral and somatic nerves which are shown in more than one third of the models. Of particular relevance is a representation of human brain convolutions preceding the one published by Rolando in 1830, and an extremely accurate and detailed preparartion of the sympathetic and parasympathetic systems. An overall evaluation of the collection greatly emphasizes both his artistic and scientific values, reflecting the intelligent cooperation between the Florentine artist and the Sardinian anatomist

Relationships among lying and standing behaviour, body condition score and milk production in primiparous cows

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Luigi Castaldi (Pistoia 1890-Firenze 1945) and his outstanding contribution to the history of Florentine wax modelling

Luigi Castaldi a pupil of Giulio Chiarugi and promoter, in 1929, with Nello Beccari and Emerico Luna, of the Società Italiana di Anatomia was, from 1927 to 1943, Director of the Anatomy Institute of the University of Cagliari. His publications, encompassing various fields of anatomy, neuroanatomy, auxology, applied anatomy, biology, and experimental morphology were awarded with several prestigious national and international prizes. Similar acknowledgements were granted to his many publications on the History of Anatomy and Medicine. Among them, there are the biographies of Filippo Civinini (1805-1844), Filippo Pacini (1812-1883), Atto Tigri (1813-1875) and the oration given the 29th of September 1935 for the translation of the remains of these illustrious anatomists from Pistoia to the church of S. Maria delle Grazie, adjacent to the Ospedale del Ceppo, the seat of the old Medical School of Pistoia. Nowadays, the most well known of his historical studies, regarded as a true classic, is the masterly essay: “Francesco Antonio Boi primo cattedratico di anatomia a Cagliari e le cere fiorentine di Clemente Susini”. The book, published by L Olschki posthumously in 1947 through the good offices of his friends, and still present in the catalogue of the original publisher, is scrupulously supported by documents found in the archives of Cagliari and Florence. Besides illustrating the figure of FA Boi the Sardinian Anatomist who, by order of Carlo Felice of Savoy, commissioned the wax models for the University of Cagliari to Clemente Susini, Castaldi gives a vivid and unprecedented description of La Specola Museum, and of the personalities responsible for its establishment. Moreover, though highly praising the outstanding scientific achievements of Felice Fontana, for the first time, he ascribes to Clemente Susini the wax modelling, formerly known as the work of Fontana