Cytotoxic effects of Gemcitabine-loaded liposomes in human anaplastic thyroid carcinoma cells

BACKGROUND: Identification of effective systemic antineoplastic drugs against anaplastic thyroid carcinomas has particularly important implications. In fact, the efficacy of the chemotherapeutic agents presently used in these tumours, is strongly limited by their low therapeutic index. METHODS: In this study gemcitabine was entrapped within a pegylated liposomal delivery system to improve the drug antitumoral activity, thus exploiting the possibility to reduce doses to be administered in cancer therapy. The cytotoxic effects of free or liposome-entrapped gemcitabine was evaluated against a human thyroid tumour cell line. ARO cells, derived from a thyroid anaplastic carcinoma, were exposed to different concentrations of the drug. Liposomes formulations were made up of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine/cholesterol/1,2-distearoyl-sn-glycero-3-phosphoethanolamine-MPEG (8:3:1 molar ratio). Cell viability was assessed by both trypan bleu dye exclusion assay and fluorimetric analysis of cell DNA content. RESULTS: A cytotoxic effect of free gemcitabine was present only after 72 h incubation (ARO cell mortality increased of approximately 4 fold over control at 1 μM, 7 fold at 100 μM). When gemcitabine was encapsulated in liposomes, a significant effect was observed by using lower concentrations of the drug (increased cell mortality of 2.4 fold vs. control at 0.3 μM) and earlier exposure time (24 h). CONCLUSION: These findings show that, in vitro against human thyroid cancer cells, the gemcitabine incorporation within liposomes enhances the drug cytotoxic effect with respect to free gemcitabine, thus suggesting a more effective drug uptake inside the cells. This may allow the use of new formulations with lower dosages (side effect free) for the treatment of anaplastic human thyroid tumours

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Early management of adult traumatic spinal cord injury in patients with polytrauma: a consensus and clinical recommendations jointly developed by the World Society of Emergency Surgery (WSES) & the European Association of Neurosurgical Societies (EANS).

BACKGROUND: The early management of polytrauma patients with traumatic spinal cord injury (tSCI) is a major challenge. Sparse data is available to provide optimal care in this scenario and worldwide variability in clinical practice has been documented in recent studies. METHODS: A multidisciplinary consensus panel of physicians selected for their established clinical and scientific expertise in the acute management of tSCI polytrauma patients with different specializations was established. The World Society of Emergency Surgery (WSES) and the European Association of Neurosurgical Societies (EANS) endorsed the consensus, and a modified Delphi approach was adopted. RESULTS: A total of 17 statements were proposed and discussed. A consensus was reached generating 17 recommendations (16 strong and 1 weak). CONCLUSIONS: This consensus provides practical recommendations to support a clinician's decision making in the management of tSCI polytrauma patients

Características da fonetografia em indivíduos com equilíbrio dentofacial pós-muda vocal Characteristics of phonetography on subjects with dentofacial balance in vocal post mutation

OBJETIVO: caracterizar, por meio de fonetografia, o perfil da extensão vocal em indivíduos sem alterações pós-muda vocal e equilíbrio dentofacial. MÉTODO: participaram deste estudo 15 homens com idades entre 14 e 35 anos com pós-muda vocal. Eles responderam a um questionário específico, e também foram submetidos a uma avaliação antropométrica da face, a avaliação dento-oclusal, o exame fonetografia e também a uma análise da frequência fundamental habitual da voz. RESULTADOS: frequência fundamental mínima: 89Hz ± 3Hz ou 29st ±14st; Frequência fundamental máxima: 665Hz±179Hz ou 63st±5st; Extensão Vocal: 34st±6st; Intensidade mínima: 66 dB ± 3dB; Intensidade máxima: 114dB ± 5dB; Extensão Dinâmica Máxima: 42dB ± 4dB, Área do Fonetograma: 936,4 dB.st ± 258,8 dB.st ou 42,1 cm² ± 11,6 cm²; Frequência Fundamental Habitual para a vogal "a": 111,26 Hz ± 15,24 Hz. CONCLUSÃO: apesar de os estudos nacionais e internacionais apresentados neste trabalho não considerarem a condição dentofacial dos indivíduos, os resultados foram semelhantes.<br>PURPOSE: to characterize, by means of phonetography, the profile of voice extension in individuals with post changes, dentofacial balanced voice. METHOD: fifteen male individuals participated in this study, in vocal postmutation, aged between 14 and 35 years old. They answered a specific self-response questionnaire, and they were also submitted to an anthropometric assessment of the face, dento-occlusal evaluation, phonetography examination and to an analysis of the usual fundamental frequency of the voice. RESULTS: minimum Fundamental Frequency: =89Hz±3Hz or =29st±14st, Maximum Fundamental Frequency: X=665Hz±179Hz or X=63st±5, Voice Extension: X=34st±6st, Minimum Intensity: X=66dB±3dB, Maximum Intensity: X=114dB±5dB, Maximum Dynamic Extension: X=42dB±4dB, Phonetogram Area: X=936,4dB.st±258,8dB.st or X=42,1cm²±11,6cm², Usual Fundamental Frequency of the "a" vowel: X=111,26Hz±15,24Hz. CONCLUSION: although national and international studies presented in this work do not consider the dentofacial condition of the subjects, the results were very similar