Inhibition of Transient Receptor Potential Vanilloid 6 channel, elevated in human ovarian cancers, reduces tumour growth in a xenograft model.

Transient Receptor Potential Vanilloid 6 (TRPV6), a non-voltage gated calcium channel, is implicated in malignancies and correlates with Gleason scores in prostate cancer and with poor prognosis in breast cancer. Data on the TRPV6 status of ovarian malignancies has not received significant attention. The effect of inhibiting TRPV6 activity on ovarian tumour growth has never been reported.

First-in-human phase I study of SOR-C13, a TRPV6 calcium channel inhibitor, in patients with advanced solid tumors.

Introduction This was an open-label, dose escalation (3 + 3 design), Phase I study of SOR-C13 in patients with advanced tumors of epithelial origin. Primary objectives were to assess safety/tolerability and pharmacokinetics. Secondary goals were to assess pharmacodynamics and efficacy of SOR-C13.

Antimicrobial properties of MX-2401, an expanded-spectrum lipopeptide active in the presence of lung surfactant.

MX-2401 is an expanded-spectrum lipopeptide antibiotic selective for Gram-positive bacteria that is a semisynthetic analog of the naturally occurring lipopeptide amphomycin. It was active against Enterococcus spp., including vancomycin-sensitive Enterococcus (VSE), vanA-, vanB-, and vanC-positive vancomycin-resistant Enterococcus (VRE), linezolid- and quinupristin-dalfopristin-resistant isolates (MIC(90) of 4 μg/ml), methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive S.

Mechanism of action and limited cross-resistance of new lipopeptide MX-2401.

MX-2401 is a semisynthetic calcium-dependent lipopeptide antibiotic (analogue of amphomycin) in preclinical development for the treatment of serious Gram-positive infections. In vitro and in vivo, MX-2401 demonstrates broad-spectrum bactericidal activity against Gram-positive organisms, including antibiotic-resistant strains. The objective of this study was to investigate the mechanism of action of MX-2401 and compare it with that of the lipopeptide daptomycin.

Antimicrobial and antifungal activities of a novel cationic antimicrobial peptide, omiganan, in experimental skin colonisation models.

Omiganan pentahydrochloride is a novel, synthetic, cationic, antimicrobial peptide that is being developed for the prevention of catheter-related infections and the treatment of acne and rosacea. In this study, the efficacy of topical omiganan gel was evaluated in two skin colonisation models (ex vivo pig skin and in vivo guinea pig skin). When tested in the ex vivo pig skin colonisation model, omiganan 0.

Omiganan pentahydrochloride in the front line of clinical applications of antimicrobial peptides.

Ribosomally synthesized antimicrobial peptides have very wide killing spectra and bacterial resistance to these peptides seems to be a rare phenomenon. Indolicidin is a ribosomally synthesized antimicrobial peptide that served as a template to omiganan, which is in development for the prevention of catheter-related bloodstream infections; clinical trials also proved its efficiency against acne vulgaris. Omiganan is the most advanced molecule in the front line of clinical applications of antimicrobial peptides.

Semisynthetic approaches to laspartomycin analogues.

Laspartomycin C (1), a lipopeptide antibiotic related to amphomycin, consists of a cyclic peptide core and an aspartic acid unit external to the core and linking this to a C15-2,3-unsaturated fatty acid. This was reported initially to be active against Staphylococcus aureus, and more recent studies have shown that it is active against VRE, VISA, and MRSA isolates. The enzymatic cleavage of the fatty acid tail was accomplished with a deacylase produced by Actinoplanes utahensis and resulted in two peptides, designated Peptide 1 and Peptide 2.

Presence of the LEE (locus of enterocyte effacement) in pig attaching and effacing Escherichia coli and characterization of eae, espA, espB and espD genes of PEPEC (pig EPEC) strain 1390.

In the present study, attaching and effacing Escherichia coli (AEEC) O45 isolates from post-weaning pigs with diarrhoea were examined for the presence of the LEE (locus of enterocyte effacement) using various DNA probes derived from the LEE of human enteropathogenic E. coli (EPEC) strain E2348/69. The LEE fragment was conserved among the eae -positive pig isolates.

Characterization of a periplasmic ATP-binding cassette iron import system of Brachyspira (Serpulina) hyodysenteriae.

The nucleotide sequence of the pathogenic spirochete Brachyspira hyodysenteriae bit (for "Brachyspira iron transport") genomic region has been determined. The bit region is likely to encode an iron ATP-binding cassette transport system with some homology to those encountered in gram-negative bacteria. Six open reading frames oriented in the same direction and physically linked have been identified.

Genomic relatedness among Actinobacillus pleuropneumoniae field strains of sterotypes 1 and 5 isolated from healthy and diseased pigs.

Forty-four Actinobacillus pleuropneumoniae isolates recovered from both healthy and diseased pigs were characterized by random amplified polymorphic DNA analysis (RAPD), pulsed field gel electrophoresis (PFGE) and apx toxin gene typing. Nine RAPD types and 14 PFGE patterns were identified. No common RAPD or PFGE patterns were found between strains of serotype 1 and those of serotype 5.

Chromosome sizes and phylogenetic relationships between serotypes of Actinobacillus pleuropneumoniae.

The genome size of Actinobacillus pleuropneumoniae was determined by pulsed field gel electrophoresis of AscI and ApaI digested chromosomal DNA. The genome size of the type strain 4074T (serotype 1) was determined to be 2404 +/- 40 kb. The chromosome sizes for the reference strains of the other serotypes range between 2.

Cloning and characterization of a dextranase gene (dexS) from Streptococcus suis.

A gene (dexS) coding for a Streptococcus suis capsular type 2 dextranase (DexS) was detected in a recombinant gene library constructed in phage lambda ZapII, and its nucleotide sequence was determined. Sequence comparison showed that the dexS gene product had significant similarities with enzymes which hydrolyze glucose polymers. Moreover, conserved amino acids that are suggested to be part of the active site of the glucosidases are also found in DexS.

Characterization of Serpulina hyodysenteriae isolates of serotypes 8 and 9 by random amplification of polymorphic DNA analysis.

A PCR-based DNA fingerprinting method termed RAPD (Random Amplification of Polymorphic DNA), or AP-PCR (for Arbitrary Primed PCR) was used to detect sequence diversity among reference strains and isolates of Serpulina hyodysenteriae. RAPD fingerprinting of 20 S. hyodysenteriae isolates of serotypes 8 or 9 from Quebec was generated with 2 different 10-base primers used independently.

Localization of conserved B-cell epitopes among encapsulated and non-encapsulated Haemophilus influenzae P2 porin proteins using synthetic peptides.

The P2 outer membrane protein of Haemophilus influenzae belongs to a class of apparently ubiquitous proteins in Gram-negative bacteria that function as porins. Murine hybridomas raised to the P2 protein and synthetic peptides were used to investigate the structural and antigenic relationships among P2 proteins of encapsulated and non-encapsulated H. influenzae.