The Dark Side of the Salad: Salmonella typhimurium Overcomes the Innate Immune Response of Arabidopsis thaliana and Shows an Endopathogenic Lifestyle

Salmonella enterica serovar typhimurium contaminated vegetables and fruits are considerable sources of human infections. Bacteria present in raw plant-derived nutrients cause salmonellosis, the world wide most spread food poisoning. This facultative endopathogen enters and replicates in host cells and actively suppresses host immune responses. Although Salmonella survives on plants, the underlying bacterial infection mechanisms are only poorly understood. In this report we investigated the possibility to use Arabidopsis thaliana as a genetically tractable host system to study Salmonella-plant interactions. Using green fluorescent protein (GFP) marked bacteria, we show here that Salmonella can infect various Arabidopsis tissues and proliferate in intracelullar cellular compartments. Salmonella infection of Arabidopsis cells can occur via intact shoot or root tissues resulting in wilting, chlorosis and eventually death of the infected organs. Arabidopsis reacts to Salmonella by inducing the activation of mitogen-activated protein kinase (MAPK) cascades and enhanced expression of pathogenesis related (PR) genes. The induction of defense responses fails in plants that are compromised in ethylene or jasmonic acid signaling or in the MKK3-MPK6 MAPK pathway. These findings demonstrate that Arabidopsis represents a true host system for Salmonella, offering unique possibilities to study the interaction of this human pathogen with plants at the molecular level for developing novel drug targets and addressing current safety issues in human nutrition

Targeted therapies in colorectal cancer: an integrative view by PPPM

In developed countries, colorectal cancer (CRC) is the third most common malignancy, but it is the second most frequent cause of cancer-related death. Clinicians are still faced with numerous challenges in the treatment of this disease, and future approaches which target the molecular features of the disorder will be critical for success in this disease setting. Genetic analyses of many solid tumours have shown that up to 100 protein-encoding genes are mutated. Within CRC, numerous genetic alterations have been identified in a number of pathways. Therefore, understanding the molecular pathology of CRC may present information on potential routes for treatment and may also provide valuable prognostic information. This will be particularly pertinent for molecularly targeted treatments, such as anti-vascular endothelial growth factor therapies and anti-epidermal growth factor receptor (EGFR) monoclonal antibody therapy. KRAS and BRAF mutations have been shown to predict response to anti-EGFR therapy. As EGFR can also signal via the phosphatidylinositol 3-kinase (PI3K) kinase pathway, there is considerable interest in the potential roles of members of this pathway (such as PI3K and PTEN) in predicting treatment response. Therefore, a combined approach of new techniques that allow identification of these biomarkers alongside interdisciplinary approaches to the treatment of advanced CRC will aid in the treatment decision-making process and may also serve to guide future therapeutic approaches

Prognostic significance of miR-34 rs4938723 T > C polymorphism in triple negative breast cancer patients

Objectives: The aim of this was the assessment of the prognostic role of the rs4938723 C > T polymorphism of the miR-34 in triple negative breast cancer patients. Methods: Therefore formalin fixed paraffin embedded tissue samples from 114 triple negative breast cancer patients and blood samples from 124 healthy donors were genotyped and subsequently extensive statistical analysis was performed in order to investigate the clinical value of this polymorphism in triple negative breast cancer. Results: Our statistical analysis disclosed that the majority of patients harboring ductal breast carcinoma (69.4%) have the TC or CC genotypes (P = .020). Moreover the survival of the patients was significantly correlated with the occurrence of the TC or CC alleles (P < .001). Regarding the correlation of miR-34 polymorphisms with patients' survival we found that women with TC or CC single nucleotide polymorphisms were characterized by shorter disease free survival intervals (P = .05). Furthermore triple negative breast cancer patients with TC/CC genotype exhibited shorter overall survival intervals as disclosed by Kaplan Meier analysis (P < .001) and Cox regression analysis (HR = 3.2, %95 CI = 2.0–5.5, P = .008). Stratified Kaplan-Meier analysis showed that the women harboring the TC or CC genotype along with the ductal histology had significantly shorter survival (P < .001). This result was also confirmed by Univariate Cox regression analysis, which showed that women ductal breast cancer and TC or CC genotype are of worse prognosis (HR = 2.35, %95 CI = 2.1–4.65, P = .003). Conclusions: In conclusion, we found that the TC and CC alleles are associated with unfavorable prognosis in triple negative breast cancer patients. © 2019 The Canadian Society of Clinical Chemist