Search results for "AZO"
showing 10 items of 5680 documents
Central nervous system involvement in ALK-rearranged NSCLC : promising strategies to overcome crizotinib resistance
2016
ABSTRACT: Introduction: ALK rearranged Non Small Cell Lung Cancers (NSCLCs) represent a distinct subgroup of patients with peculiar clinic-pathological features. These patients exhibit dramatic responses when treated with the ALK tyrosine kinase inhibitor Crizotinib, albeit Central Nervous System (CNS) activity is much less impressive than that observed against extracranial lesions. CNS involvement has become increasingly observed in these patients, given their prolonged survival. Several novel generation ALK inhibitors have been developing to increase CNS penetration and to provide more complete ALK inhibition. Areas covered: The CNS activity of Crizotinib and novel generation ALK inhibito…
Use of Cardioprotective Dexrazoxane Is Associated with Increased Myelotoxicity in Anthracycline-Treated Soft-Tissue Sarcoma Patients
2019
<b><i>Background:</i></b> Dexrazoxane (DEX) is indicated as a cardioprotective agent for breast cancer patients receiving the anthracycline doxorubicin. Two meta-analyses in metastatic breast cancer reported an apparent increase in the severity of myelosuppression when DEX was used. So far, no data in soft-tissue sarcoma (STS) patients are available. <b><i>Methods:</i></b> We retrospectively analyzed hematological toxicity data from 133 consecutive STS patients who received a chemotherapy regimen containing an anthracycline and ifosfamide (AI) in the perioperative or metastatic settings between January 2006 and December 2017. Of these, 46 rece…
Blockade of nitric oxide signalling promotes resilience to the effects of social defeat stress on the conditioned rewarding properties of MDMA in mice
2020
Abstract MDMA abuse continues being a serious problem in our society. Environmental factors, such as stress, increase the vulnerability of individuals to develop drug abuse and we have observed that exposure to social defeat (SD) stress alters the sensitivity of mice to the rewarding effects of MDMA in the conditioned place preference (CPP) paradigm. In the present study, we evaluated the role of the nitric oxide (NO) pathway in the effects of SD on the rewarding properties of MDMA. Three groups of mice were treated with an inhibitor of NO synthesis, 7-nitroindazole (0, 7.25 and 12.5 mg/kg), before each exposure to SD and place conditioning with MDMA (1.25 mg/kg) on PND 54, 56, 58, and 60. …
Moving Towards Precision Urologic Oncology: Targeting Enzalutamide-resistant Prostate Cancer and Mutated Forms of the Androgen Receptor Using the Nov…
2017
Abstract Darolutamide (ODM-201) is a novel androgen receptor (AR) antagonist with a chemical structure distinctly different from currently approved AR antagonists that targets both wild-type and mutated ligand binding domain variants to inhibit AR nuclear translocation. Here, we evaluate the activity of darolutamide in enzalutamide-resistant castration resistant prostate cancer (CRPC) as well as in AR mutants detected in patients after treatment with enzalutamide, abiraterone, or bicalutamide. Darolutamide significantly inhibited cell growth and AR transcriptional activity in enzalutamide-resistant MR49F cells in vitro, and led to decreased tumor volume and serum prostate-specific antigen l…
Is prolonged infusion of piperacillin/tazobactam and meropenem in critically ill patients associated with improved pharmacokinetic/pharmacodynamic an…
2016
Objectives: We utilized the database of the Defining Antibiotic Levels in Intensive care unit patients (DALI) study to statistically compare the pharmacokinetic/pharmacodynamic and clinical outcomes between prolonged- infusion and intermittent-bolus dosing of piperacillin/tazobactam and meropenem in critically ill patients using inclusion criteria similar to those used in previous prospective studies. Methods: This was a post hoc analysis of a prospective, multicentre pharmacokinetic point-prevalence study (DALI), which recruited a large cohort of critically ill patients from 68 ICUs across 10 countries. Results: Of the 211 patients receiving piperacillin/tazobactam and meropenem in the DAL…
Inter-individual differences in the susceptibility of primary human hepatocytes towards drug-induced cholestasis are compound and time dependent.
2018
Abstract Cholestasis represents a major subtype of drug-induced liver injury and novel preclinical models for its prediction are needed. Here we used primary human hepatocytes (PHH) from different donors in 2D-sandwich (2D-sw) and/or 3D-spheroid cultures to study inter-individual differences in the response towards cholestatic hepatotoxins after short-term (48–72 hours) and long-term repeated exposures (14 days). The cholestatic liabilities of drugs were determined by comparing cell viability upon exposure to the highest non-cytotoxic drug concentration in the presence and absence of a non-cytotoxic concentrated bile acid mixture. In 2D-sw culture, cyclosporine A and amiodarone presented cl…
Nonacidic Farnesoid X Receptor Modulators.
2017
As a cellular bile acid sensor, farnesoid X receptor (FXR) participates in regulation of bile acid, lipid and glucose homeostasis, and liver protection. Clinical results have validated FXR as therapeutic target in hepatic and metabolic diseases. To date, potent FXR agonists share a negatively ionizable function that might compromise their pharmacokinetic distribution and behavior. Here we report the development and characterization of a high-affinity FXR modulator not comprising an acidic residue.
Community-acquired febrile urinary tract infection caused by extended-spectrum beta-lactamase-producing bacteria in hospitalised infants.
2015
Abstract Introduction Extended-spectrum beta-lactamase (ESBL) producing bacteria are infrequent pathogens of urinary tract infections in children. The objective of our study was to investigate the presence, clinically associated characteristics and risk factors for acquisition of urinary tract infection/acute pyelonephritis (UTI/APN) in hospitalised children Methods A case-control study in a second level community hospital in Spain, in which 537 episodes of UTI/APN were investigated in a retrospective study between November 2005 and August 2014. Cases were patients with ESBL strains. For each case, four ESBL-negative controls were selected. A questionnaire with the variables of interest was…
Pazopanib for treatment of typical solitary fibrous tumours: a multicentre, single-arm, phase 2 trial
2020
[Background] Solitary fibrous tumour is an ultra-rare sarcoma, which encompasses different clinicopathological subgroups. The dedifferentiated subgroup shows an aggressive course with resistance to pazopanib, whereas in the malignant subgroup, pazopanib shows higher activity than in previous studies with chemotherapy. We designed a trial to test pazopanib activity in two different cohorts of solitary fibrous tumour: the malignant-dedifferentiated cohort, which was previously published, and the typical cohort, which is presented here.
The collagen type I segment long spacing (SLS) and fibrillar forms: Formation by ATP and sulphonated diazo dyes.
2016
The collagen type I segment long spacing (SLS) crystallite is a well-ordered rod-like molecular aggregate, ∼300nm in length, which is produced in vitro under mildly acidic conditions (pH 2.5-3.5) in the presence of 1mM ATP. The formation of the SLS crystallite amplifies the inherent linear structural features of individual collagen heterotrimers, due to the punctate linear distribution and summation of the bulkier amino acid side chains along the length of individual collagen heterotrimers. This can be correlated structurally with the 67nm D-banded collagen fibril that is found in vivo, and formed in vitro. Although first described many years ago, the range of conditions required for ATP-in…