Genomic Landscape of Vinflunine Response in Metastatic Urothelial Cancer.

Background And Aims: Metastatic urothelial carcinoma (mUC) remains an incurable disease with limited treatment options after platinum-based chemotherapy and immune checkpoint blockade (ICB). Vinflunine has shown a modest increase in overall survival and remains a therapeutic option for chemo- and immunotherapy refractory tumours. However, biomarkers that could identify responding patients to vinflunine and possible alternative therapies after failure to treatment are still missing.

The Inactivation of Enzymes Belonging to the Central Carbon Metabolism Is a Novel Mechanism of Developing Antibiotic Resistance.

Fosfomycin is a bactericidal antibiotic, analogous to phosphoenolpyruvate, that exerts its activity by inhibiting the activity of MurA. This enzyme catalyzes the first step of peptidoglycan biosynthesis, the transfer of enolpyruvate from phosphoenolpyruvate to uridine-diphosphate--acetylglucosamine. Fosfomycin is increasingly being used, mainly for treating infections caused by Gram-negative multidrug-resistant bacteria.

Differential development of large-cell neuroendocrine or small-cell lung carcinoma upon inactivation of 4 tumor suppressor genes.

High-grade neuroendocrine lung malignancies (large-cell neuroendocrine cell carcinoma, LCNEC, and small-cell lung carcinoma, SCLC) are among the most deadly lung cancer conditions with no optimal clinical management. The biological relationships between SCLC and LCNEC are still largely unknown and a current matter of debate as growing molecular data reveal high heterogeneity with potential therapeutic consequences. Here we describe murine models of high-grade neuroendocrine lung carcinomas generated by the loss of 4 tumor suppressors.

The intrinsic resistome of Klebsiella pneumoniae.

Molecular epidemiology studies aiming at understanding the acquisition of antimicrobial resistance by clinical isolates of Klebsiella pneumoniae are regularly published; however, information on the genes that contribute to its characteristic phenotype of resistance to antibiotics (intrinsic resistome) is scarce. To fill this gap, a K. pneumoniae transposon mutant library was screened and 171 mutants presenting changes in their susceptibility to antibiotics were selected, in which the transposon insertion site was determined in 75.

Liquid Biopsy Biomarkers in Bladder Cancer: A Current Need for Patient Diagnosis and Monitoring.

Bladder Cancer (BC) represents a clinical and social challenge due to its high incidence and recurrence rates, as well as the limited advances in effective disease management. Currently, a combination of cytology and cystoscopy is the routinely used methodology for diagnosis, prognosis and disease surveillance. However, both the poor sensitivity of cytology tests as well as the high invasiveness and big variation in tumour stage and grade interpretation using cystoscopy, emphasizes the urgent need for improvements in BC clinical guidance.

Genome-wide analysis shows that RNase G plays a global role in the stability of mRNAs in Stenotrophomonas maltophilia.

Gene expression is determined by critical processes such as RNA synthesis and degradation. Ribonucleases participate in the coordinated and differential decay of messenger RNAs. We describe a suitable method of normalization and calculation of mRNAs half-life values quantified by RNA-Seq.

Bacterial Multidrug Efflux Pumps: Much More Than Antibiotic Resistance Determinants.

Bacterial multidrug efflux pumps are antibiotic resistance determinants present in all microorganisms. With few exceptions, they are chromosomally encoded and present a conserved organization both at the genetic and at the protein levels. In addition, most, if not all, strains of a given bacterial species present the same chromosomally-encoded efflux pumps.

The analysis of the antibiotic resistome offers new opportunities for therapeutic intervention.

Most efforts in the development of antimicrobials have focused on the screening of lethal targets. Nevertheless, the constant expansion of antimicrobial resistance makes the antibiotic resistance determinants themselves suitable targets for finding inhibitors to be used in combination with antibiotics. Among them, inhibitors of antibiotic inactivating enzymes and of multidrug efflux pumps are suitable candidates for improving the efficacy of antibiotics.

Use of phenotype microarrays to study the effect of acquisition of resistance to antimicrobials in bacterial physiology.

It is widely accepted that the acquisition of resistance to antimicrobials confers a fitness cost. Different works have shown that the effect of acquiring resistance in bacterial physiology may be more specific than previously thought. Study of these specific changes may help to predict the outcome of resistant organisms in different ecosystems.

The inactivation of RNase G reduces the Stenotrophomonas maltophilia susceptibility to quinolones by triggering the heat shock response.

Quinolone resistance is usually due to mutations in the genes encoding bacterial topoisomerases. However, different reports have shown that neither clinical quinolone resistant isolates nor in vitro obtained Stenotrophomonas maltophilia mutants present mutations in such genes. The mechanisms so far described consist on efflux pumps' overexpression.

WIP regulates persistence of cell migration and ruffle formation in both mesenchymal and amoeboid modes of motility.

The spatial distribution of signals downstream from receptor tyrosine kinases (RTKs) or G-protein coupled receptors (GPCR) regulates fundamental cellular processes that control cell migration and growth. Both pathways rely significantly on actin cytoskeleton reorganization mediated by nucleation-promoting factors such as the WASP-(Wiskott-Aldrich Syndrome Protein) family. WIP (WASP Interacting Protein) is essential for the formation of a class of polarised actin microdomain, namely dorsal ruffles, downstream of the RTK for PDGF (platelet-derived growth factor) but the underlying mechanism is poorly understood.

The intrinsic resistome of bacterial pathogens.

Intrinsically resistant bacteria have emerged as a relevant health problem in the last years. Those bacterial species, several of them with an environmental origin, present naturally low-level susceptibility to several drugs. It has been proposed that intrinsic resistance is mainly the consequence of the impermeability of cellular envelopes, the activity of multidrug efflux pumps or the lack of appropriate targets for a given family of drugs.

[Neonatal cholestasis and hypoglycemia like form of congenital hypopituitarism presentation].

Congenital hypopituitarism is a rare disease, of variable clinic. The neonatal hypoglycemia is one of the habitual forms of presentation; the cholestasis is a rare symptom of this disease. This is the case of a 2-months-old infant hospitalized for cholestatic jaundice.