TYROSINE KINASE INHIBITORS IN ADVANCED THYROID CANCER

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Stato nutrizionale e risposta al trattamento con inibitori tirosino-chinasici nel carcinoma tiroideo avanzato

L’utilizzo di inibitori tirosino-chinasici (TKI) rappresenta un’importante opzione terapeutica nel trattamento del carcinoma tiroideo metastatico. Il trattamento con tali farmaci è frequentemente associato alla comparsa di eventi avversi che possono compromettere uno stato nutrizionale già precario, tipico di questi pazienti, peggiorandone quindi anche la prognosi. Diversi studi hanno valutato l’impatto dello stato nutrizionale e della presenza di sarcopenia sulla risposta al trattamento e sulla sopravvivenza dei pazienti oncologici. Tali parametri sembrano correlare con la prognosi e la sopravvivenza nei pazienti oncologici

The genome sequence and transcriptome of Potentilla micrantha and their comparison to Fragaria vesca (the woodland strawberry)

Background The genus Potentilla is closely related to that of Fragaria, the economically important strawberry genus. Potentilla micrantha is a species that does not develop berries, but shares numerous morphological and ecological characteristics with F. vesca. These similarities make P. micrantha an attractive choice for comparative genomics studies with F. vesca Findings In this study, the Potentilla micrantha genome was sequenced and annotated, and RNA-Seq data from the different developmental stages of flowering and fruiting were used to develop a set of gene predictions. A 327 Mbp sequence and annotation of the genome of P. micrantha, spanning 2,674 sequence contigs, with an N50 size of 335,712, estimated to cover 80% of the total genome size of the species was developed. The genus Potentilla has a characteristically larger genome size than Fragaria, but the recovered sequence scaffolds were remarkably collinear at the micro-syntenic level with the genome of F. vesca, its closest sequenced relative. A total of 33,602 genes were predicted, and 95.1% of BUSCO genes were complete within the presented sequence. Thus, we argue that the majority of the gene-rich regions of the genome have been sequenced Conclusions Comparisons of RNA-Seq data from the stages of floral and fruit development revealed genes differentially expressed between P. micrantha and F. vesca. The data presented are a valuable resource for future studies of berry development in Fragaria and the Rosaceae and they also shed light on the evolution of genome size and organization in this family

Exploring mobility in Italian Neolithic and Copper Age communities

As a means for investigating human mobility during late the Neolithic to the Copper Age in central and southern Italy, this study presents a novel dataset of enamel oxygen and carbon isotope values (δ18Oca and δ13Cca) from the carbonate fraction of biogenic apatite for one hundred and twenty-six individual teeth coming from two Neolithic and eight Copper Age communities. The measured δ18Oca values suggest a significant role of local sources in the water inputs to the body water, whereas δ13Cca values indicate food resources, principally based on C3 plants. Both δ13Cca and δ18Oca ranges vary substantially when samples are broken down into local populations. Statistically defined thresholds, accounting for intra-site variability, allow the identification of only a few outliers in the eight Copper Age communities, suggesting that sedentary lifestyle rather than extensive mobility characterized the investigated populations. This seems to be also typical of the two studied Neolithic communities. Overall, this research shows that the investigated periods in peninsular Italy differed in mobility pattern from the following Bronze Age communities from more northern areas

Improvement of Overall Survival Using TKIs as Salvage Therapy in Advanced Thyroid Carcinoma: Real-Life Data on a Single Center Experience

Background: Tyrosine kinase inhibitors (TKIs) have improved progression-free survival in patients with advanced thyroid cancer. So far, few studies have investigated the efficacy of TKIs in a second-line setting. The purpose of our study was to explore the salvage therapy efficacy in patients with advanced thyroid cancer. Methods: We retrospectively evaluated 63 patients with progressive advanced thyroid carcinoma treated with TKIs divided into a Study group (23 patients) treated with salvage therapy, and a Control group (40 patients) treated with only one TKI. Results: Similar clinical benefits (stable disease + partial response) and progression free survival between the first and the second line TKI were observed in the Study group (p > 0.99 and p = 0.5, respectively). Median overall survival (OS) was 67.7 months in the Study group and 22.6 months in the Control group (HR 2.46; 95% CI 1.34–4.52, p = 0.004). After stratifying the whole population by age (<65 and ≥65 years), OS was significantly different (p < 0.001) with the best survival curve in younger patients, treated with salvage therapy and the worst in older subjects, treated with only one TKI. Conclusions: Salvage therapy showed a significant improvement of OS in patients with advanced thyroid cancer who experienced disease progression during prior TKI therapies

Attiggio di Fabriano (Ancona): la ceramica

gLI aUTORI ILLUSTRANO I MATERIALI CERAMICI DEL SITO NEO-ENEOLITICO DI aTTIGGIO DI FABRIAN

Blockade of the programmed death ligand 1 (PD-L1) as potential therapy for anaplastic thyroid cancer

Purpose: Anaplastic thyroid carcinoma (ATC) is a rare, highly aggressive form of thyroid cancer (TC) characterized by an aggressive behavior and poor prognosis, resulting in patients’ death within a year. Standard treatments, such as chemo and radiotherapy, as well as tyrosine kinase inhibitors, are ineffective for ATC treatment. Cancer immunotherapy is one of the most promising research area in oncology. The PD-1/PD-L1 axis is of particular interest, in light of promising data showing a restoration of host immunity against tumours, with the prospect of long-lasting remissions. Methods: In this study, we evaluated PD-L1 expression in a large series of TCs (20 cases) showing a progressive dedifferentiation of the thyroid tumour from well differentiated TC to ATC, employing two different antibodies [R&D Systems and VENTANA PD-L1 (SP263) Rabbit Monoclonal Primary Antibody]. We also tested the anti PD-L1 mAb in an in vivo animal model. Results: We found that approximately 70-90% of ATC cases were positive for PD-L1 whereas normal thyroid and differentiated TC were negative. Moreover, all analyzed cases presented immunopositive staining in the endothelium of vessels within or in close proximity to the tumour, while normal thyroid vessels were negative. PD-L1 mAb was also effective in inhibiting ATC growth in an in vivo model. Conclusions: These data suggest that immunotherapy may be a promising treatment specific for ATC suggesting the need to start with clinical TRIALs