Concordance of c-kit mutational status in matched primary and metastatic cutaneous canine mast cell tumors at baseline

BackgroundMutation analysis of proto-oncogene c-kit (c-kit) is advisable before starting treatment with tyrosine kinase inhibitors in dogs with mast cell tumor (MCT), including those with metastatic disease. Testing is usually performed on primary tumors, assuming that c-kit mutation status does not change in metastasis.Hypothesis/ObjectivesTo give an insight into the mutational processes and to make a recommendation on the use of c-kit mutational analysis in the clinical setting.AnimalsTwenty-one client-owned dogs with metastatic MCT.MethodsDogs undergoing resection or biopsy for both primary and matched metastatic MCT were prospectively enrolled. Total RNA or DNA was extracted from primary MCT and corresponding metastases. Exons 8, 9, and 11 were amplified by PCR and sequenced. Genetic features between primary MCT and metastases were compared. Their correlation with clinicopathologic features was investigated.ResultsConcordance (mutated or wild-type) of mutational status, evaluable in 21 primary and matched metastatic (20 nodal and 1 splenic) MCTs, was 100%. Three new c-kit mutations were identified. No significant correlation was detected between c-kit mutation and clinicopathologic features.Conclusions and Clinical ImportanceProto-oncogene c-kit mutational status is conserved between any primary and its matched secondary tumor, suggesting that both can be used for c-kit mutational testing. Targeted therapies might be also used to treat metastatic disease

Supersymmetric gyratons in five dimensions

We obtain the gravitational and electromagnetic field of a spinning radiation beam-pulse (a gyraton) in minimal five-dimensional gauged supergravity and show under which conditions the solution preserves part of the supersymmetry. The configurations represent generalizations of Lobatchevski waves on AdS with nonzero angular momentum, and possess a Siklos-Virasoro reparametrization invariance. We compute the holographic stress-energy tensor of the solutions and show that it transforms without anomaly under these reparametrizations. Furthermore, we present supersymmetric gyratons both in gauged and ungauged five-dimensional supergravity coupled to an arbitrary number of vector supermultiplets, which include gyratons on domain walls.Comment: 25 pages, no figures, uses JHEP3.cls. Final version to appear in CQ

Biological effects of EF24, a curcumin derivative, alone or combined with mitotane in adrenocortical tumor cell lines

Background: Curcumin has numerous properties and is used in many preclinical conditions, including cancer. It has low bioavailability, while its derivative EF24 shows enhanced solubility. However, its effects have never been explored in adrenocortical tumor cell models. The efficacy of EF24 alone or combined with mitotane (reference drug for adrenocortical cancer) was evaluated in two adrenocortical tumor cell lines, SW13 and H295R. Method and Results: EF24 reduced cell viability with an IC50 (half maximal inhibitory concentration) of 6.5 \ub1 2.4 \ub5M and 4.9 \ub1 2.8 \ub5M for SW13 and H295R cells, respectively. Combination index (EF24 associated with mitotane) suggested an additivity effect in both cell lines. Cell cycle analysis revealed an increase in subG0/G1 phase, while motility assay showed a decrease in migratory cell capacity, and similarly, clonogenic assay indicated that EF24 could reduce colony numbers. Furthermore, Wnt/\u3b2-catenin, NF-\u3baB, MAPK, and PI3k/Akt pathways were modulated by Western blot analysis when treating cells with EF24 alone or combined with mitotane. In addition, intracellular reactive oxygen species levels increased in both cell lines. Conclusion: This work analyzed EF24 in adrenocortical tumor cell lines for the first time. These results suggest that EF24 could potentially impact on adrenocortical tumors, laying the foundation for further research in animal models

The transcriptional regulator ZNF398 mediates pluripotency and epithelial character downstream of TGF-beta in human PSCs

Human pluripotent stem cells (hPSCs) have the capacity to give rise to all differentiated cells of the adult. TGF-beta is used routinely for expansion of conventional hPSCs as flat epithelial colonies expressing the transcription factors POU5F1/OCT4, NANOG, SOX2. Here we report a global analysis of the transcriptional programme controlled by TGF-beta followed by an unbiased gain-of-function screening in multiple hPSC lines to identify factors mediating TGF-beta activity. We identify a quartet of transcriptional regulators promoting hPSC self-renewal including ZNF398, a human-specific mediator of pluripotency and epithelial character in hPSCs. Mechanistically, ZNF398 binds active promoters and enhancers together with SMAD3 and the histone acetyltransferase EP300, enabling transcription of TGF-beta targets. In the context of somatic cell reprogramming, inhibition of ZNF398 abolishes activation of pluripotency and epithelial genes and colony formation. Our findings have clear implications for the generation of bona fide hPSCs for regenerative medicine

Black strings in AdS_5

We present non-extremal magnetic black string solutions in five-dimensional gauged supergravity. The conformal infinity is the product of time and S^1xS_h, where S_h denotes a compact Riemann surface of genus h. The construction is based on both analytical and numerical techniques. We compute the holographic stress tensor, the Euclidean action and the conserved charges of the solutions and show that the latter satisfy a Smarr-type formula. The phase structure is determined in the canonical ensemble, and it is shown that there is a first order phase transition from small to large black strings, which disappears above a certain critical magnetic charge that is obtained numerically. For another particular value of the magnetic charge, that corresponds to a twisting of the dual super Yang-Mills theory, the conformal anomalies coming from the background curvature and those arising from the coupling to external gauge fields exactly cancel. We also obtain supersymmetric solutions describing waves propagating on extremal BPS magnetic black strings, and show that they possess a Siklos-Virasoro reparametrization invariance.Comment: 40 pages, 7 figures, JHEP3. v2: minor corrections, 2 references added. v3: typos in holographic stress tensor corrected, 3 references adde

Aroma de vinhos Lorena elaborados com diferentes leveduras.

A liberação dos terpenos em uvas moscatéis, pela ação de glicosidases das leveduras, pode aumentar e/ou modificar o aroma de vinhos. Este experimento comparou as características sensoriais de vinhos BRS Lorena (Malvasia Bianca x Seyval) elaborados com diferentes leveduras.Resumo

The Therapeutic Potential of Anthocyanins : Current Approaches Based on Their Molecular Mechanism of Action

Anthocyanins are natural phenolic pigments with biological activity. They are well-known to have potent antioxidant and antiinflammatory activity, which explains the various biological effects reported for these substances suggesting their antidiabetic and anticancer activities, and their role in cardiovascular and neuroprotective prevention. This review aims to comprehensively analyze different studies performed on this class of compounds, their bioavailability and their therapeutic potential. An in-depth look in preclinical, in vitro and in vivo, and clinical studies indicates the preventive effects of anthocyanins on cardioprotection, neuroprotection, antiobesity as well as their antidiabetes and anticancer effects

Malformazioni artero-venose del distretto cervico-facciale. Diagnosi e metodi di trattamento

Obiettivo. Gli Autori, dopo una revisione della Letteratura, presentano i risultati di uno studio eseguito su pazienti affetti da malformazione artero-venose del distretto cervico facciale. Metodi. Tredici pazienti affetti da malformazioni artero-venose del distretto cervico facciale sono stati trattati presso la Cattedra e Divisione di Chirurgia Maxillo-Facciale di Parma dal 1995 al 2000. La malformazione in cinque pazienti si \ue8 manifestata in et\ue0 infantile, in cinque in adolescenza ed in tre in et\ue0 adulta. Le malformazioni artero-venose sono state classificate in base alla stadiazione clinica di Schobinger. Quattro pazienti sono stati trattati con embolizzazione superselettiva della lesione, uno con resezione chirurgica ed i rimanenti otto con embolizzazione superselettiva seguita da resezione chirurgica radicale della malformazione. I pazienti sono stati sottoposti ad un attento follow-up per un periodo da 2 a 5 anni. Risultati. I casi trattati con resezione chirurgica e quelli trattati con embolizzazione superselettiva seguita da resezione chirurgica non hanno dato segni di recidiva; mentre solo uno dei pazienti trattati con embolizzazione superselettiva ha ottenuto un risultato soddisfacente ottenendo la scomparsa della sintomatologia dolorosa e l'arresto delle frequenti emorragie a livello locale. Questo tipo di trattamento pu\uf2 infatti essere un utile palliativo per il trattamento del dolore e del sanguinamento nei casi in cui la resezione chirurgica provocherebbe danni estetici molto importanti. \uc8 opportuno, in seguito, controllare con attenzione il comportamento della lesione trattata con la sola embolizzazione in quanto potrebbe andare incontro ad un rapido aumento di volume con ricomparsa della sintomatologia. Conclusioni. Alla luce della nostra esperienza, in accordo con la Letteratura, il trattamento di scelta non sempre pu\uf2 essere l'embolizzazione seguita dalla resezione chirurgica. In base alle caratteristiche cliniche della lesione devono essere scelti trattamenti diversi (embolizzazione, resezione chirurgica, embolizzazione seguita da resezione) al fine di ottenere il migliore risultato possibile.BACKGROUND: After a review of the literature, the results of a clinical study carried out on cases of extracranial arteriovenous malformations of the head and neck, are reported. METHODS: Thirteen patients with extracranial arteriovenous malformations of the head and neck have been treated at the Maxillofacial Department of the University of Parma from 1995 to 2000. Five patients observed the onset in childhood, five in adolescence and three in adulthood. Arteriovenous malformations have been classified according to Schobinger's clinical staging. Four patients with superselective embolization, one with surgical resection and the remaining eight with superselective embolization followed by radical en bloc resection have been treated. The follow-up period varied from 2 to 5 years. RESULTS: No relapses have been observed in the cases treated with surgical resection and with superselective embolization followed by radical excision. Only 1 patient treated by superselective embolization had a good outcome. This treatment can be a good palliative in the treatment pain and bleeding particularly when surgical excision would result in mutilation or disfigurement, nevertheless it is necessary a careful follow-up since the lesion treated only by superselective embolization can grow quickly and begin bleeding and aching again. CONCLUSIONS: In personal experience, according to the literature, embolic/surgical management of arteriovenous malformations is not always the treatment of choice. On the basis of clinical characteristics of the lesions, different kinds of treatments (embolization, resection, embolization followed by resection) may be chosen to obtain favorable RESULTS