Targeting stromal remodeling and cancer stem cell plasticity overcomes chemoresistance in triple negative breast cancer

The cellular and molecular basis of stromal cell recruitment, activation and crosstalk in carcinomas is poorly understood, limiting the development of targeted anti-stromal therapies. In mouse models of triple negative breast cancer (TNBC), Hedgehog ligand produced by neoplastic cells reprograms cancer-associated fibroblasts (CAFs) to provide a supportive niche for the acquisition of a chemo-resistant, cancer stem cell (CSC) phenotype via FGF5 expression and production of fibrillar collagen. Stromal treatment of patient-derived xenografts with smoothened inhibitors (SMOi) downregulates CSC markers expression and sensitizes tumors to docetaxel, leading to markedly improved survival and reduced metastatic burden. In the phase I clinical trial EDALINE, 3 of 12 patients with metastatic TNBC derived clinical benefit from combination therapy with the SMOi Sonidegib and docetaxel chemotherapy, with one patient experiencing a complete response. These studies identify Hedgehog signaling to CAFs as a novel mediator of CSC plasticity and an exciting new therapeutic target in TNBC.Aurélie S. Cazet, Mun N. Hui, Benjamin L. Elsworth, Sunny Z. Wu, Daniel Roden ... Michael S. Samuel ... et al

Microbiological and chemical monitoring of Marsala base wine obtained by spontaneous fermentation during large-scale production

The present work was undertaken to evaluate the effect of the natural winemaking on the microbial and chemical composition of Marsala base wine. To this purpose, a large-scale vinification process of Grillo grape cultivar was monitored from harvesting to the final product. Total yeasts (TY) showed a rapid increase after must pressing and reached values almost superimposable to those registered during the conventional winemakings. Lactic acid bacteria (LAB) were registered at the highest levels simultaneously to yeast growth at the beginning of the process. Saccharomyces cerevisiae was the species found at the highest concentrations in all samples analysed. Several strains (n= 16) was registered at high levels during the alcoholic fermentation and/or aging of wine; only two of them were detected on the grape surface. Lactobacillus plantarum was the LAB species most frequently isolated during the entire vinification process. Ethanol content was approximately 14% (v/v) at the end of vinification. The value of pH did not greatly vary during the process and the volatile acidity (VA) was detected at low concentrations during the entire transformation. The concentration of malic acid rapidly decreased during the AF; on the other hand, lactic acid showed an irregular trend during the entire process. trans-caffeil tartaric acid was the most abundant hydroxycinnamoyl tartaric acid and volatile organic compounds (VOC) were mainly represented by isoamylic alcohol and isobutanol

Detection of antimicrobial activities and bacteriocin structural genes in faecal enterococci of wild animals

The production of antimicrobial activities as well as the presence of bacteriocin structural genes (entA, entB, entP, entQ, cylL, entAS-48, bac31, and entL50A/B) were studied in 140 non-selected faecal enterococcal isolates recovered from wild animals. Eight different indicator strains (including Listeria monocytogenes, Pediococcus pentosaceus, and different enterococcal species) were used for antimicrobial activity detection. Twenty-five of the 140 enterococci (18%) showed antimicrobial activity against L. monocytogenes and 33 additional isolates (24%) showed antimicrobial activity against other indicator strains, but Listeria. At least one bacteriocin structural gene was detected in 17 of the 25 enterococci with antimicrobial activity against L. monocytogenes and different combinations of entA, entB, entP, entQ, entL50A/B, and cylL genes were detected; entA and entB were the most prevalent detected genes, and they were generally associated. Bacteriocin structural genes were detected in 10 of 33 isolates with antimicrobial activity against indicator strains other than Listeria, and the cylL gene was the most prevalent one, especially in E. faecalis isolates. © 2006 Elsevier GmbH. All rights reserved

Ethanol stress response in Lactobacillus plantarum WCFS1

Transcriptome profiles of control Lactobacillus plantarum WCFS1 cells were compared with 8% ethanol adapted cells and with 10 min or 30 min 8% ethanol shocked cells

Pseudomonas aeruginosa Isolates from Spanish Children: Occurrence in Faecal Samples, Antimicrobial Resistance, Virulence, and Molecular Typing

Pseudomonas aeruginosa is a major opportunistic human pathogen, responsible for nosocomial infections and infections in patients with impaired immune systems. Little data exist about the faecal colonisation by P. aeruginosa isolates in healthy humans. The occurrence, antimicrobial resistance phenotype, virulence genotype, and genetic lineages of P. aeruginosa from faecal samples of children from two different Spanish regions were characterised. Seventy-two P. aeruginosa were isolated from 1,443 faecal samples. Low antimicrobial resistance levels were detected: ceftazidime (8%), cefepime (7%), aztreonam (7%), gentamicin (3%), ciprofloxacin (1%), and imipenem (1%); susceptibility to meropenem, amikacin, tobramycin, levofloxacin, and colistin. Four multidrug-resistant strains were found. Important differences were detected between both geographical regions. Forty-one sequence types were detected among the 48 tested strains. Virulence and quorum sensing genes were analysed and 13 virulotypes were detected, being 26 exoU-positive strains. Alteration in protein OprD showed eight different patterns. The unique imipenem-resistant strain showed a premature stop codon in OprD. Intestinal colonisation by P. aeruginosa, mainly by international clones (as ST244, ST253, and ST274), is an important factor for the systemic infections development and the environmental dissemination. Periodic active surveillance is useful to identify these community human reservoirs and to control the evolution of antibiotic resistance and virulence activity. © 2018 Lidia Ruiz-Roldán et al

Ethanol stress response in Lactobacillus plantarum WCFS1

Transcriptome profiles of control Lactobacillus plantarum WCFS1 cells were compared with 8% ethanol adapted cells and with 10 min or 30 min 8% ethanol shocked cells

Ethanol stress response in Lactobacillus plantarum WCFS1

Transcriptome profiles of control Lactobacillus plantarum WCFS1 cells were compared with 8% ethanol adapted cells and with 10 min or 30 min 8% ethanol shocked cells