Risk factors for quinolone-resistance in women presenting with Escherichia coli acute pyelonephritis

In France, according to the National Epidemiology Observatory of Bacterial Resistance to Antibiotics, 15.3% of outpatient urinary Escherichia coli isolates were fluoroquinolone-resistant in 2010. This puts to question the relevance of empirical fluoroquinolone therapy for community-acquired acute pyelonephritis (APN), potentially severe infections.     

Design,Synthesis, and Optimization of Balanced Dual NK1/NK3 Receptor Antagonists

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DNA hypermethylation is associated with invasive phenotype of malignant melanoma

Tumor cell invasion is one of the key processes during cancer progression, leading to life-threatening metastatic lesions in melanoma. As methylation of cancer-related genes plays a fundamental role during tumorigenesis and may lead to cellular plasticity which promotes invasion, our aim was to identify novel epigenetic markers on selected invasive melanoma cells. Using Illumina BeadChip assays and Affymetrix Human Gene 1.0 microarrays, we explored the DNA methylation landscape of selected invasive melanoma cells and examined the impact of DNA methylation on gene expression patterns. Our data revealed predominantly hypermethylated genes in the invasive cells affecting the neural crest differentiation pathway and regulation of the actin cytoskeleton. Integrative analysis of the methylation and gene expression profiles resulted in a cohort of hypermethylated genes (IL12RB2, LYPD6B, CHL1, SLC9A3, BAALC, FAM213A, SORCS1, GPR158, FBN1 and ADORA2B) with decreased expression. On the other hand, hypermethylation in the gene body of the EGFR and RBP4 genes was positively correlated with overexpression of the genes. We identified several methylation changes that can have role during melanoma progression, including hypermethylation of the promoter regions of the ARHGAP22 and NAV2 genes that are commonly altered in locally invasive primary melanomas as well as during metastasis. Interestingly, the down-regulation of the methylcytosine dioxygenase TET2 gene, which regulates DNA methylation, was associated with hypermethylated promoter region of the gene. This can probably lead to the observed global hypermethylation pattern of invasive cells and might be one of the key changes during the development of malignant melanoma cells.     

Gefitinib in advanced non-small cell lung cancer

BACKGROUND: Gefitinib is an oral, selective epidermal growth factor receptor (EGFR) inhibitor that has activity in non-small cell lung cancer (NSCLC). AIM: To evaluate the tolerability, safety-profile and response of single agent gefitinib in patients with advanced stage NSCLC. METHODS: Twenty-seven patients of good performance status with stage IIIB or IV NSCLC were entered on the study at the Sydney Cancer Centre. Gefitinib was prescribed at an oral dose of 250 mg daily, as a continuous dose. Radiological evaluation of indicator lesions occurred at baseline and were repeated every 2-3 months until disease progression. Toxicity was graded using standard measures at baseline and at every month. RESULTS: The response rate was 17% in the patients eligible for evaluation. Symptom improvement was observed in 75% of patients. No patients withdrew because of adverse events. Toxicity was observed in 15 patients and consisted mainly of rash (59%), which was usually mild in severity. CONCLUSION: Gefitinib is active in NSCLC. It is well tolerated with minimal side-effects. Symptomatic improvement was found in the majority of patients treated with gefitinib. There may be a role for gefitinib in the palliation of symptoms in patients with advanced NSCLC.     

Antigenic and immunogenic mimicry of the HER2/neu oncoprotein by phage-displayed peptides

To recover peptides that antigenically and immunogenically mimic the p185^HER2 oncoprotein, we selected the phage-peptide libraries pVIII-9aa and pVIII-9aa. Cys using murine monoclonal antibodies (mAb) MGr2 and MGr6, directed against two distinct epitopes of the p185^HER2 extracellular domain. Phagedisplayed peptides containing consensus amino acid motifs were recovered and shown to compete specifically for mAb binding on tumor cells that overexpress p185^HER2. The deduced amino acid sequence of the peptides suggests that both epitopes defined by the mAb on p185^HER2 are discontinuous and that hydrophobic interactions are involved in binding with the mAb. A phage clone displaying the GPLDSLFAQ peptide elicited a specific immune response against the p185^HER2 in BALB/c mice, demonstrating that this phage-displayed peptide represents an immunological equivalent of the MGr2 epitope on p185^HER2 and might be used as a substitute for this oncoprotein in in vitro and in vivo immunological studies.