Search results for "DISEASES"

FGFR a promising druggable target in cancer: Molecular biology and new drugs.

2017

Abstract: Introduction: The Fibroblast Growth Factor Receptor (FGFR) family consists of Tyrosine Kinase Receptors (TKR) involved in several biological functions. Recently, alterations of FGFR have been reported to be important for progression and development of several cancers. In this setting, different studies are trying to evaluate the efficacy of different therapies targeting FGFR. Areas Covered: This review summarizes the current status of treatments targeting FGFR, focusing on the trials that are evaluating the FGFR profile as inclusion criteria: Multi-Target, Pan-FGFR Inhibitors and anti-FGF (Fibroblast Growth Factor)/FGFR Monoclonal Antibodies. Expert opinion: Most of the TKR share …

Survey on the presence of A. simplex s.s. and A. pegreffii hybrid forms in Central-Western Mediterranean Sea

2016

Abstract In this study, 1029 fish and cephalopod samples came from Central-Western Mediterranean (FAO 37.1.1 and FAO 37.1.3) were analysed for Anisakidae larvae research with the aim to identify possible hybridisations between Anisakis pegreffii and Anisakis simplex s.s. species. A total of 1765 larvae were detected, with prevalence values between 8.1% and 100%. The morphologic analysis revealed characters attributable to morphotype I of Anisakis in 98.5% of the examined larvae, while 1.5% belonged to the morphotype II. PCR-based Restriction Fragment Length Polymorphism (PCR–RFLP) analysis of the entire ITS region (ITS1, 5.8S and ITS2) of nuclear ribosomal DNA (rDNA) was performed with Hinf…

Intensive aquaculture selects for increased virulence and interference competition in bacteria

2016

Although increased disease severity driven by intensive farming practices is problematic in food production, the role of evolutionary change in disease is not well understood in these environments. Experiments on parasite evolution are traditionally conducted using laboratory models, often unrelated to economically important systems. We compared how the virulence, growth and competitive ability of a globally important fish pathogen, Flavobacterium columnare , change under intensive aquaculture. We characterized bacterial isolates from disease outbreaks at fish farms during 2003–2010, and compared F. columnare populations in inlet water and outlet water of a fish farm during the 2010 outbre…

Henneguya zschokkei (Myxozoa) infection in cultured whitefish: Age-dependence, seasonality and distribution within host

2017

Abstract Whitefish ( Coregonus lavaretus ) is an important species for European fisheries and aquaculture. Recently, the myxosporean Henneguya zschokkei has been observed to infect the muscles of whitefish in fish farms. Plasmodia of H. zschokkei prevent marketing of the fillet and cause economic losses. The factors associated with occurrence of the parasite in fish farms have not been investigated previously. We studied age-dependence, seasonality, and within-host distribution of H. zschokkei plasmodia in farmed whitefish by examining a total of 1599 fish. Distribution of plasmodia within the fish was not uniform. When the fillet was divided into parts, the number of plasmodia was positive…

Efficacy and Determinants of Response to HER Kinase Inhibition in HER2-Mutant Metastatic Breast Cancer

2020

Abstract HER2 mutations define a subset of metastatic breast cancers with a unique mechanism of oncogenic addiction to HER2 signaling. We explored activity of the irreversible pan-HER kinase inhibitor neratinib, alone or with fulvestrant, in 81 patients with HER2-mutant metastatic breast cancer. Overall response rate was similar with or without estrogen receptor (ER) blockade. By comparison, progression-free survival and duration of response appeared longer in ER+ patients receiving combination therapy, although the study was not designed for direct comparison. Preexistent concurrent activating HER2 or HER3 alterations were associated with poor treatment outcome. Similarly, acquisition of m…

Diversity of extracellular vesicles from different developmental stages of Fasciola hepatica

2020

The secretion of extracellular vesicles (EVs) in Fasciola hepatica adult worms was described by our group in 2012. Since then, EVs have been found in other helminths, thus providing a new paradigm for the complete understanding of host-parasite communication. However, information was lacking regarding the possible existence and role of EVs from other developmental stages of the parasite. In this study, we confirm the secretion of EVs by F. hepatica eggs and juvenile forms. EVs were isolated by size exclusion chromatography and characterised by nanoparticle tracking analysis and electron microscopy. We observed a large diversity in the morphologies of these EVs, suggesting specific functions…

Coexpresión de NG2/GFAP tras la diferenciación en células transfectadas con las mutaciones de GFAP y en células procedentes de gliomas indiferenciados

2020

Resumen: Introducción: La enfermedad de Alexander es una enfermedad rara causada por mutaciones en el gen que codifica la proteína glial ácida fibrilar (GFAP). En un estudio previo hemos observado que la diferenciación de neuroesferas transfectadas con estas mutaciones genera un tipo celular que comparte la expresión de GFAP y NG2. Objetivos: Determinar el efecto de las mutaciones en marcadores moleculares en comparación con células de glioma diferenciados que expresan simultáneamente GFAP y NG2. Métodos: Se utilizaron muestras de glioblastoma humana (GLM) y neuroesferas procedentes de rata transfectadas con mutaciones de GFAP para el análisis de la expresión tras diferenciación de GFAP y N…

2017

Many quinazoline derivatives have been synthesized over the last few decades with great pharmacological potential, such as antimalarial, anti-inflammatory, antimicrobial, anticancer, and antiviral. But so far, no quinazoline–artemisinin hybrids have been reported in the literature. In the present study, five novel quinazoline–artemisinin hybrids were synthesized and evaluated for their in vitro biological activity against malarial parasites (Plasmodium falciparum 3D7), leukemia cells (CCRF-CEM and CEM/ADR5000), and human cytomegalovirus. Remarkably, hybrid 9 (EC50 = 1.4 nM), the most active antimalarial compound of this study, was not only more potent than artesunic acid (EC50 = 9.7 nM) but…

Microevolutionary response of a gut nematode to intestinal inflammation.

2017

7 pages; International audience; Parasitic helminths interfere with the immune response of their hosts to establish long-lasting, chronic infections. While favorable to the parasite, the capacity to dampen the immune response can also provide a benefit to the host in terms of reduced risk of immune disorders and immunopathology. The immunomodulatory role of nematodes has been exploited in clinical trials to treat a number of inflammatory and immune diseases. However, how parasites adapt to an inflammatory environment remains a poorly explored question. Here, we conducted a serial passage experiment where the gut nematode Heligmosomoides polygyrus was maintained for nine generations in mice …

Redox signaling in the gastrointestinal tract.

2017

Redox signaling regulates physiological self-renewal, proliferation, migration and differentiation in gastrointestinal epithelium by modulating Wnt/β-catenin and Notch signaling pathways mainly through NADPH oxidases (NOXs). In the intestine, intracellular and extracellular thiol redox status modulates the proliferative potential of epithelial cells. Furthermore, commensal bacteria contribute to intestine epithelial homeostasis through NOX1- and dual oxidase 2-derived reactive oxygen species (ROS). The loss of redox homeostasis is involved in the pathogenesis and development of a wide diversity of gastrointestinal disorders, such as Barrett's esophagus, esophageal adenocarcinoma, peptic ulc…