Search results for "22"

When Three Isn't a Crowd: A Digyny Concept for Treatment-Resistant, Near-Triploid Human Cancers.

2019

Near-triploid human tumors are frequently resistant to radio/chemotherapy through mechanisms that are unclear. We recently reported a tight association of male tumor triploidy with XXY karyotypes based on a meta-analysis of 15 tumor cohorts extracted from the Mitelman database. Here we provide a conceptual framework of the digyny-like origin of this karyotype based on the germline features of malignant tumors and adaptive capacity of digyny, which supports survival in adverse conditions. Studying how the recombinatorial reproduction via diploidy can be executed in primary cancer samples and HeLa cells after DNA damage, we report the first evidence that diploid and triploid cell sub-populati…

MUC1 deficiency mediates corticosteroid resistance in chronic obstructive pulmonary disease.

2018

Background Lung inflammation in COPD is poorly controlled by inhaled corticosteroids (ICS). Strategies to improve ICS efficacy or the search of biomarkers who may select those patients candidates to receive ICS in COPD are needed. Recent data indicate that MUC1 cytoplasmic tail (CT) membrane mucin can mediate corticosteroid efficacy in chronic rhinosinusitis. The objective of this work was to analyze the previously unexplored role of MUC1 on corticosteroid efficacy in COPD in vitro and in vivo models. Methods MUC1-CT expression was measured by real time PCR, western blot, immunohistochemistry and immunofluorescence. The inflammatory mediators IL-8, MMP9, GM-CSF and MIP3α were measured by EL…

A multicentre, phase IIa study of zolbetuximab as a single agent in patients with recurrent or refractory advanced adenocarcinoma of the stomach or l…

2019

Abstract Background Claudin 18.2 (CLDN18.2) is physiologically confined to gastric mucosa tight junctions; however, upon malignant transformation, perturbations in cell polarity lead to CLDN18.2 epitopes being exposed on the cancer cell surface. The first-in-class monoclonal antibody, zolbetuximab (formerly known as IMAB362), binds to CLDN18.2 and can induce immune-mediated lysis of CLDN18.2-positive cells. Patients and methods Patients with advanced gastric, gastro-oesophageal junction (GEJ) or oesophageal adenocarcinomas with moderate-to-strong CLDN18.2 expression in ≥50% of tumour cells received zolbetuximab intravenously every 2 weeks for five planned infusions. At least three patients …

Dopaminergic-GABAergic interplay and alcohol binge drinking

2019

© 2019 Elsevier Ltd The dopamine D 3 receptor (D 3 R), in the nucleus accumbens (NAc), plays an important role in alcohol reward mechanisms. The major neuronal type within the NAc is the GABAergic medium spiny neuron (MSN), whose activity is regulated by dopaminergic inputs. We previously reported that genetic deletion or pharmacological blockade of D 3 R increases GABA A α6 subunit in the ventral striatum. Here we tested the hypothesis that D 3 R-dependent changes in GABA A α6 subunit in the NAc affect voluntary alcohol intake, by influencing the inhibitory transmission of MSNs. We performed in vivo and ex vivo experiments in D 3 R knockout (D 3 R −/− ) mice and wild type littermates (D 3 …

Pulmonary Strongyloides stercoralis infection.

2016

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.

How do skeletal morbidity rate and special toxicities affect 12-week versus 4-week schedule zoledronic acid efficacy? A systematic review and a meta-…

2019

Abstract Background Zoledronic Acid is a bisphosphonate used in a 4-week schedule for the treatment of bone metastases. Some randomized trials supported its role also when administered every 12 weeks. Methods we performed a systematic review and a meta-analysis in order to evaluate the two different schedules in terms of skeletal morbidity rate (SMR), skeletal related events (SRE) and adverse events (AEs). Results our results showed a clinical difference favouring the 12-week schedule in terms of AEs (RR 1.17, 95% CI 1.06–1.29). No signifcant differences were found for SMR (RR 0.97, 95% CI 0.84–1.13) and SRE (RR 1.02, 95% CI 0.89–1.16). Conclusions Our findings support in clinical practice …

Patients with advanced oral squamous cell carcinoma have high levels of soluble E-cadherin in the saliva

2017

Background: The objective of this study was to assess the potential clinical value of the concentration of soluble salivary E-cadherin (sE-cadherin) compared with the clinical value of the resence of membranous E-cadherin (mE-cadherin) in oral squamous cell carcinoma tumor tissues. Material and Methods: Data regarding patient demographics, clinical stage, saliva and tumor tissue samples were collected. The saliva was analyzed for sE-cadherin protein levels and was compared to the mE-cadherin immunohistochemical expression levels in tumor tissues, which were assessed via the HercepTest® method. Patients without cancer were included in the study as a control group for comparisons of the sE-ca…

Multidimensional Prognostic Index and pro-adrenomedullin plasma levels as mortality risk predictors in older patients hospitalized with community-acq…

2018

BACKGROUND: To evaluate the prognostic accuracy of proadrenomedullin (proADM) in comparison with and in addition to the Multidimensional Prognostic Index (MPI), a validated predictive tool for mortality derived from a comprehensive geriatric assessment (CGA) to predict one-month mortality risk in older patients hospitalized with community-acquired pneumonia (CAP). METHODS: All patients aged 65 years and older, consecutively admitted to an acute geriatric ward with a diagnosis of CAP from February to July 2012. At admission and at discharge they were submitted to a standard CGA in order to calculate MPI. Moreover, plasma samples were taken at baseline and after one, three and five days of ho…

Venetoclax or placebo in combination with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma (BELLINI): a randomis…

2020

Background Venetoclax is a highly selective, potent, oral BCL-2 inhibitor, which induces apoptosis in multiple myeloma cells. Venetoclax plus bortezomib and dexamethasone has shown encouraging clinical efficacy with acceptable safety and tolerability in a phase 1 trial. The aim of this study was to evaluate venetoclax plus bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma. Methods In this randomised, double-blind, multicentre, phase 3 trial, patients aged 18 years or older with relapsed or refractory multiple myeloma, an Eastern Cooperative Oncology Group performance status of 2 or less, who had received one to three previous therapies were enrolled from …