Cannonkirby5153
d FGFR2 fusions.Introduction Biliary tract cancers (BTCs) include four uncommon primary biliary malignancies characterized by poor prognosis intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, gallbladder cancer, and ampulla of Vater cancer. To date, the available therapeutic options are limited; nevertheless, with the advent of targeted therapy and immunotherapy, the treatment scenario is constantly changing, opening toward future possibilities for the personalized treatment of BTC. Among these treatments, nivolumab is currently being investigated in BTC. Areas covered This review provides a comprehensive overview of the recent progress and future perspectives of immunotherapy for the treatment of BTC, with a particular focus on nivolumab, which has demonstrated its effectiveness in many malignancies and is in its initial phase of evaluation in BTC. Expert opinion BTCs are not among those tumors that demonstrated remarkable sensitivity to immunotherapy, such as melanoma or non-small-cell lung cancer. However, the results obtained with nivolumab are not disappointing if we analyze the population of the trials testing its efficacy, including pretreated patients, unselected for PD-L1 expression and with different BTCs. In our opinion, ICIs such as nivolumab could fill an empty spot in the treatment of selected BTC patients, especially in combination with other agents, and the results of ongoing clinical trials are awaited.
Perphenazine (PPZ) is a typical antipsychotic that is mainly administrated for the treatment of schizophrenia. Due to its highly lipophilic nature and extensive hepatic first-pass metabolism, its oral bioavailability is low (40%).
The novel nanocarriers like solid lipid nanoparticles (SLN) have been reported to be highly effective for improving the therapeutic effect of drugs. Therefore the main scope of the present investigation was the evaluation of
characteristics of PPZ-SLN in terms of pharmacokinetic parameters and brain distribution.
The PPZ-SLN was prepared by the solvent-emulsification and evaporation method. The storage stability of PPZ-SLN and empty SLN powders was studied for 3 months.
pharmacokinetic studies and brain distribution evaluations were performed following a single oral dose administration of PPZ and PPZ-SLN suspensions on male Wistar rats. An HPLC method was established and validated for the quantitative determination of PPZ in plasma and brain samples.
The storage stability studies revealed the good storage stability of the both PPZ-SLN and empty SLN at 4 °C. Compared to PPZ suspension, the relative bioavailability and the brain distribution of PPZ-SLN were increased up to 2-fold and 16-fold, respectively. Mean residence time (MRT) and half-life (t
) of PPZ-SLN were significantly (
value < 0.01) increased in both plasma and brain homogenate compared to PPZ suspension.
The significant improvement in the pharmacokinetic properties of PPZ following one oral dose indicates that SLN is a promising drug delivery system for PPZ and shows a high potential for successful brain delivery of this antipsychotic.
The significant improvement in the pharmacokinetic properties of PPZ following one oral dose indicates that SLN is a promising drug delivery system for PPZ and shows a high potential for successful brain delivery of this antipsychotic.
Radiation-induced xerostomia is one of the most common symptoms experienced by cancer patients. The aim of our study is to evaluate the preventive and therapeutic effect of acupuncture for radiation-induced xerostomia in cancer patients.
Eight databases were searched for all published randomized clinical trials (RCTs) on acupuncture for radiation-induced xerostomia in cancer patients up to December 31, 2019. Manual searching included other conference abstracts and reference lists. Meta-analysis was conducted using Revman V.5.3, and risks of bias for included studies was assessed following the Cochrane Handbook.
Eight clinical trials (725 participants) were analyzed, and 3 were included in a meta-analysis. All included trials had a high risk of bias, such as selection, performance, and detection bias. Analysis indicated favorable effects of acupuncture regarding the improvement of xerostomia symptoms (MD -3.05,
= 0.02, 95% CI -5.58 to -0.52), compared with sham acupuncture. There were no significant d flow measurements. The evidence is still limited due to the low quality of the published studies.The well-known Two-Process Model of Sleep Regulation describes the integration of the circadian rhythm of arousal and sleep - Process C, and the homeostatic pressure to sleep - Process S. Presently, the known biological markers for Process C are melatonin and core body temperature; whereas, for Process S, there is no biological marker except that of aspects of the electroencephalogram (EEG). Endozepines are a class of endogenous compounds that act like benzodiazepines (BZ), i.e., serving as ligands for the BZ binding sites on GABAA receptors. Not much is known about the role of endozepines, in particular non-peptide endozepines, in the sleep field except very few reports about high concentrations observed in endozepine stupor, a rare phenomenon of idiopathic recurring stupor. We focused on hypoxanthine and thromboxane A2, which are considered to have endozepine function. This study aimed to examine the effect of 24 h of acute sleep deprivation on blood levels of hypoxanthine and thromboxane A2 of healthy subjects without sleep problems or disorders. The results showed a significant decrease of both compounds in the morning after sleep deprivation in comparison to the unrestricted normal sleep condition, thereby suggesting that these endozepines are secreted regularly while asleep, and, thus, are necessary for the sleep process. This study is the first to suggest a connection between specific biological markers - endozepines and Process S - in the Two-Process Model of Sleep Regulation and, furthermore, it sheds light on the possible role of endozepines in sleepiness and fatigue.
Paediatric brain tumour resection rates have been shown to correlate with outcome and, it is argued, are linked to operator volume and caseload. VX-770 datasheet The British paediatric neurosurgery community has previously debated centralisation of paediatric neuro-oncology. At the 2018 British Paediatric Neurosurgery Group (BPNG) meeting, a commitment was made to prospectively collect tumour resection data at each Neurosurgical Unit (NSU). Here we review our prospectively-collected 10-year database of the three commonest paediatric posterior fossa tumours - astrocytomas, medulloblastomas and ependymomas.
Our primary outcome was extent of resection (EOR) on post-operative MRI scans reviewed by neuro-radiologists. Secondary outcomes comprised neurosurgical morbidity including infection, need for cerebrospinal fluid (CSF) diversion and the occurrence of posterior fossa syndrome (PFS).
55 children had 62 operations, where our complete resection rates for pilocytic astrocytomas, medulloblastomas and ependymomas were 77%, 79% and 63%, respectively.
