Robertsonmoon1190

Pheochromocytoma and paraganglioma are neuroendocrine neoplasms, originating in the adrenal medulla and in parasympathetic and sympathetic autonomic nervous system ganglia, respectively. They usually present as localized tumours curable with surgery. However, these tumours may exhibit heterogeneous clinical course, ranging from no/minimal progression to aggressive (progressive/metastatic) behavior. For this setting of patients, current therapies are unsatisfactory. Immune checkpoint inhibitors have shown outstanding results for several types of solid cancers. We therefore aimed to summarize and discuss available data on efficacy and safety of current FDA-approved immune checkpoint inhibitors in patients with pheochromocytoma and paraganglioma. After an extensive search, we found 15 useful data sources (four full-published articles, four supplements of scientific journals, seven ongoing registered clinical trials). The data we detected, even with the limit of the small number of patients treated, make a great expectation on the therapeutic use of immune checkpoint inhibitors. Besides, the newly detected predictors of response will (hopefully) be of great helps in selecting the subset of patients that might benefit the most from this class of drugs. Finally, new trials are in the starting blocks, and they are expected to shed in the next future new light on a therapy, which is considered a milestone in oncology.Microwaved-induced in situ amorphization of a drug in a polymer has been suggested to follow a dissolution process, with the drug dissolving into the mobile polymer at temperatures above the glass transition temperature (Tg) of the polymer. Thus, based on the Noyes-Whitney and the Stoke-Einstein equations, the temperature and the viscosity are expected to directly impact the rate and degree of drug amorphization. By investigating two different viscosity grades of polyethylene glycol (PEG), i.e., PEG 3000 and PEG 4000, and controlling the temperature of the microwave oven, it was possible to study the influence of both, temperature and viscosity, on the in situ amorphization of the model drug celecoxib (CCX) during exposure to microwave radiation. In this study, compacts containing 30 wt% CCX, 69 wt% PEG 3000 or PEG 4000 and 1 wt% lubricant (magnesium stearate) were exposed to microwave radiation at (i) a target temperature, or (ii) a target viscosity. It was found that at the target temperature, compacts containing PEG 3000 displayed a faster rate of amorphization as compared to compacts containing PEG 4000, due to the lower viscosity of PEG 3000 compared to PEG 4000. Furthermore, at the target viscosity, which was achieved by setting different temperatures for compacts containing PEG 3000 and PEG 4000, respectively, the compacts containing PEG 3000 displayed a slower rate of amorphization, due to a lower target temperature, than compacts containing PEG 4000. In conclusion, with lower viscosity of the polymer, at temperatures above its Tg, and with higher temperatures, both increasing the diffusion coefficient of the drug into the polymer, the rate of amorphization was increased allowing a faster in situ amorphization during exposure to microwave radiation. Hereby, the theory that the microwave-induced in situ amorphization process can be described as a dissolution process of the drug into the polymer, at temperatures above the Tg, is further strengthened.Pancreatic ductal adenocarcinoma (PDAC) is traditionally associated with thrombocytosis/hypercoagulation and novel insights on platelet-PDAC "dangerous liaisons" are warranted. Here we performed an integrative omics study investigating the biological processes of mRNAs and expressed miRNAs, as well as proteins in PDAC blood platelets, using benign disease as a reference for inflammatory noise. Gene ontology mining revealed enrichment of RNA splicing, mRNA processing and translation initiation in miRNAs and proteins but depletion in RNA transcripts. Remarkably, correlation analyses revealed a negative regulation on SPARC transcription by isomiRs involved in cancer signaling, suggesting a specific "education" in PDAC platelets. Platelets of benign patients were enriched for non-templated additions of G nucleotides (#ntaG) miRNAs, while PDAC presented length variation on 3' (lv3p) as the most frequent modification on miRNAs. Additionally, we provided an actionable repertoire of PDAC and benign platelet-ome to be exploited for future studies. In conclusion, our data show that platelets change their biological repertoire in patients with PDAC, through dysregulation of miRNAs and splicing factors, supporting the presence of de novo protein machinery that can "educate" the platelet. These novel findings could be further exploited for innovative liquid biopsies platforms as well as possible therapeutic targets.Obesity and weight gain in bipolar disorder (BD) have multifactorial underlying causes such as medication side effects, atypical depressive symptomatology, genetic variants, and disturbances in the neuro-endocrinal system. Therefore, we aim to explore the associations between food craving (FC), clinical parameters, psychotropic medication, and appetite-related hormones. In this cross-sectional investigation, 139 individuals with BD and 93 healthy controls (HC) completed the food craving inventory (FCI). In addition, blood samples (including leptin and acylated ghrelin) were analyzed and sociodemographic and anthropometric data were collected. Individuals with BD reported higher frequencies of total FC as well as craving for fat and fast food than HC. Additionally, we found a significant negative correlation between FC and ghrelin levels in BD. Smokers with BD reported significantly more craving for high fat foods than non-smokers. Age was significantly associated with FC independent of group. Individuals with BD taking olanzapine and quetiapine reported higher frequencies of craving for sweet food, while patients currently taking lithium reported less total FC compared to those without lithium therapy. Selleck A-485 Likewise, patients currently taking valproate reported less total FC and less craving for sweets than those not taking valproate. FC appears to be of clinical relevance in individuals with BD. Contrary to previous data, this does not seem to be a female phenomenon only and might encompass more than the specific craving for carbohydrates. Although due to the cross sectional design, causality cannot be determined, the association between depressive symptomatology and fast food craving warrants further research.