GLUT1 expression in malignant tumors and its use as an immunodiagnostic marker

OBJECTIVE: To analyze glucose transporter 1 expression patterns in malignant tumors of various cell types and evaluate their diagnostic value by immunohistochemistry. INTRODUCTION: Glucose is the major source of energy for cells, and glucose transporter 1 is the most common glucose transporter in humans. Glucose transporter 1 is aberrantly expressed in several tumor types. Studies have implicated glucose transporter 1 expression as a prognostic and diagnostic marker in tumors, primarily in conjunction with positron emission tomography scan data. METHODS: Immunohistochemistry for glucose transporter 1 was performed in tissue microarray slides, comprising 1955 samples of malignant neoplasm from different cell types. RESULTS: Sarcomas, lymphomas, melanomas and hepatoblastomas did not express glucose transporter 1. Fortyseven per cent of prostate adenocarcinomas were positive, as were 29% of thyroid, 10% of gastric and 5% of breast adenocarcinomas. Thirty-six per cent of squamous cell carcinomas of the head and neck were positive, as were 42% of uterine cervix squamous cell carcinomas. Glioblastomas and retinoblastomas showed membranous glucose transporter 1 staining in 18.6% and 9.4% of all cases, respectively. Squamous cell carcinomas displayed membranous expression, whereas adenocarcinomas showed cytoplasmic glucose transporter 1 expression. CONCLUSION: Glucose transporter 1 showed variable expression in various tumor types. Its absence in sarcomas, melanomas, hepatoblastomas and lymphomas suggests that other glucose transporters mediate the glycolytic pathway in these tumors. The data suggest that glucose transporter 1 is a valuable immunohistochemical marker that can be used to identify patients for evaluation by positron emission tomography scan. The function of cytoplasmic glucose transporter 1 in adenocarcinomas must be further examined

Genetic variability and phospholipase production of<i>Malassezia pachydermatis</i>isolated from dogs with diverse grades of skin lesions

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Second-generation anticoagulant rodenticides in the blood of obligate and facultative European avian scavengers

The widespread use of second-generation anticoagulant rodenticides (SGARs) and their high persistence in animal tissues has led to these compounds becoming ubiquitous in rodent-predator-scavenger food webs. Exposure to SGARs has usually been investigated in wildlife species found dead, and despite growing evidence of the potential risk of secondary poisoning of predators and scavengers, the current worldwide exposure of free-living scavenging birds to SGARs remains scarcely investigated. We present the first active monitoring of blood SGAR concentrations and prevalence in the four European obligate (i.e., vultures) and facultative (red and black kites) avian scavengers in NE Spain. We analysed 261 free-living birds and detected SGARs in 39.1% (n = 102) of individuals. Both SGAR prevalence and concentrations (ΣSGARs) were related to the age and foraging behaviour of the species studied. Black kites showed the highest prevalence (100%), followed by red kites (66.7%), Egyptian (64.2%), bearded (20.9%), griffon (16.9%) and cinereous (6.3%) vultures. Overall, both the prevalence and average ΣSGARs were higher in non-nestlings than nestlings, and in species such as kites and Egyptian vultures foraging in anthropic landscapes (e.g., landfill sites and livestock farms) and exploiting small/medium-sized carrions. Brodifacoum was most prevalent (28.8%), followed by difenacoum (16.1%), flocoumafen (12.3%) and bromadiolone (7.3%). In SGAR-positive birds, the ΣSGAR (mean ± SE) was 7.52 ± 0.95 ng mL−1; the highest level detected being 53.50 ng mL−1. The most abundant diastereomer forms were trans-bromadiolone and flocoumafen, and cis-brodifacoum and difenacoum, showing that lower impact formulations could reduce secondary exposures of non-target species. Our findings suggest that SGARs can bioaccumulate in scavenging birds, showing the potential risk to avian scavenging guilds in Europe and elsewhere. We highlight the need for further studies on the potential adverse effects associated with concentrations of SGARSs in the blood to better interpret active monitoring studies of free-living birds.POV and AM were funded within the framework of the project RTI2018- 099609-B-C22, from the I + D + I National Plan funded by the Ministry of Science, Innovation and Universities. SGAR analyses have been performed with the own resources obtained from the Service of Toxicological Analysis at IREC (CGP170122, University of Castilla-La Mancha). PRC benefited from a contract of the Research Plan of the University of Castilla-La Mancha funded by European Fund for the Regional Development

Novel CaLB-like Lipase Found Using ProspectBIO, a Software for Genome-Based Bioprospection

Enzymes have been highly demanded in diverse applications such as in the food, pharmaceutical, and industrial fuel sectors. Thus, in silico bioprospecting emerges as an efficient strategy for discovering new enzyme candidates. A new program called ProspectBIO was developed for this purpose as it can find non-annotated sequences by searching for homologs of a model enzyme directly in genomes. Here we describe the ProspectBIO software methodology and the experimental validation by prospecting for novel lipases by sequence homology to Candida antarctica lipase B (CaLB) and conserved motifs. As expected, we observed that the new bioprospecting software could find more sequences (1672) than a conventional similarity-based search in a protein database (733). Additionally, the absence of patent protection was introduced as a criterion resulting in the final selection of a putative lipase-encoding gene from Ustilago hordei (UhL). Expression of UhL in Pichia pastoris resulted in the production of an enzyme with activity towards a tributyrin substrate. The recombinant enzyme activity levels were 4-fold improved when lowering the temperature and increasing methanol concentrations during the induction phase in shake-flask cultures. Protein sequence alignment and structural modeling showed that the recombinant enzyme has high similarity and capability of adjustment to the structure of CaLB. However, amino acid substitutions identified in the active pocket entrance may be responsible for the differences in the substrate specificities of the two enzymes. Thus, the ProspectBIO software allowed the finding of a new promising lipase for biotechnological application without the need for laborious and expensive conventional bioprospecting experimental steps

TESS asteroseismology of the known red-giant host stars HD 212771 and HD 203949

International audienc

Effects of dose modifications on the safety and efficacy of dacomitinib for EGFR mutation-positive non-small-cell lung cancer

Aim: We evaluated reasons for dacomitinib dose reduction (DR) and examined adverse event (AE) incidence, key efficacy end points (progression-free survival [PFS]/overall survival [OS]), and pharmacokinetics in dose-reducing patients in the ARCHER 1050 trial. Patients & methods: Newly diagnosed patients with EGFR mutation-positive, advanced non-small-cell lung cancer received oral dacomitinib (45 mg once-daily [QD]), with stepwise toxicity-managing DR (30 and 15 mg QD) permitted. Results: Skin toxicities (62.7%) were the most common DR-leading AEs. The AE incidence and severity decreased following DRs. Initial plasma dacomitinib exposure (45 mg QD) was generally lower in patients remaining at 45 mg QD compared with dose-reducing patients. Median PFS and OS were similar in all dacomitinib-treated patients and dose-reducing patients. Conclusion: Tolerability-guided dose modifications enabled patients to continue with dacomitinib and benefit from PFS/OS improvement

Cold atmospheric plasma, a novel approach against bladder cancer, with higher sensitivity for the high-grade cell line

Antitumor therapies based on Cold Atmospheric Plasma (CAP) are an emerging medical field. In this work, we evaluated CAP effects on bladder cancer. Two bladder cancer cell lines were used, HT-1376 (stage III) and TCCSUP (stage IV). Cell proliferation assays were performed evaluating metabolic activity (MTT assay) and protein content (SRB assay). Cell viability, cell cycle, and mitochondrial membrane potential (Δψm) were assessed using flow cytometry. Reactive oxygen and nitrogen species (RONS) and reduced glutathione (GSH) were evaluated by fluorescence. The assays were carried out with different CAP exposure times. For both cell lines, we obtained a significant reduction in metabolic activity and protein content. There was a decrease in cell viability, as well as a cell cycle arrest in S phase. The Δψm was significantly reduced. There was an increase in superoxide and nitric oxide and a decrease in peroxide contents, while GSH content did not change. These results were dependent on the exposure time, with small differences for both cell lines, but overall, they were more pronounced in the TCCSUP cell line. CAP showed to have a promising antitumor effect on bladder cancer, with higher sensitivity for the high-grade cell line.info:eu-repo/semantics/publishedVersio