Bone metastatic prostate cancer and resistance to tyrosine kinase inhibitors: an intimate relationship between loss of miR-203 and up-regulation of EGFR signaling

A tumor suppressor role for miR-203 in RAS-dependent prostate cancer metastasis has been described recently by our group. We have explored the regulatory mechanisms by which miR-203 is being regulated through EGFR signaling. We investigated the molecular mechanism of metastasis and identified novel roles of genes that interact with miR-203 downstream of activated Ras. We showed an amplifying regulatory loop involving the direct interaction of miR-203 with the EGFR ligands, AREG, EREG, and TGFA 3’UTR. Using clinical specimens and database analysis, our data suggested that decreasing miR-203 and increasing EGFR ligands, AREG, EREG, and TGFA expressions are correlated with prostate cancer progression. Since tyrosine kinase inhibitors (TKIs) have been shown to inhibit tyrosine phosphorylation of EGFR in a dose-dependent manner, we examined a role for miR-203 in TKIs-induced apoptosis in RAS-activated prostate cancer. We investigated the mechanisms by which miR-203 overexpression contributes to TKIs-resistant RAS-activated prostate cancer cells apoptosis. We have shown indications for candidate miR-203 targets that are either influenced by anti-apoptotic proteins (e.g. API5, BIRC2, and TRIAP1) or positively influenced by a novel NF-κB-inducible oncogenic molecule, TNFAIP8. These observations suggest that the latter category may be synergistically affected by the regulatory loop of miR-203 depletion and anti-apoptotic proteins overexpression. Our results provided evidence showing a role of miR-203 in regulating the expression of EGFR signaling genes in response to TKIs-resistance during prostate cancer progression

Bone metastatic prostate cancer and resistance to tyrosine kinase inhibitors: an intimate relationship between loss of miR-203 and up-regulation of EGFR signaling: DOI: 10.14800/rd.345

A tumor suppressor role for miR-203 in RAS-dependent prostate cancer metastasis has been described recently by our group. We have explored the regulatory mechanisms by which miR-203 is being regulated through EGFR signaling. We investigated the molecular mechanism of metastasis and identified novel roles of genes that interact with miR-203 downstream of activated Ras. We showed an amplifying regulatory loop involving the direct interaction of miR-203 with the EGFR ligands, AREG, EREG, and TGFA 3’UTR. Using clinical specimens and database analysis, our data suggested that decreasing miR-203 and increasing EGFR ligands, AREG, EREG, and TGFA expressions are correlated with prostate cancer progression. Since tyrosine kinase inhibitors (TKIs) have been shown to inhibit tyrosine phosphorylation of EGFR in a dose-dependent manner, we examined a role for miR-203 in TKIs-induced apoptosis in RAS-activated prostate cancer. We investigated the mechanisms by which miR-203 overexpression contributes to TKIs-resistant RAS-activated prostate cancer cells apoptosis. We have shown indications for candidate miR-203 targets that are either influenced by anti-apoptotic proteins (e.g. API5, BIRC2, and TRIAP1) or positively influenced by a novel NF-?B-inducible oncogenic molecule, TNFAIP8. These observations suggest that the latter category may be synergistically affected by the regulatory loop of miR-203 depletion and anti-apoptotic proteins overexpression. Our results provided evidence showing a role of miR-203 in regulating the expression of EGFR signaling genes in response to TKIs-resistance during prostate cancer progression

Individual variations in intestinal microbiota were higher in preterm infants with necrotising enterocolitis than healthy controls

International audienc

Establishment and development of the intestinal microbiota of preterm infants in a Lebanese tertiary hospital

© 2016 The Authors The establishment and development of the intestinal microbiota is known to be associated with profound short- and long-term effects on the health of full-term infants (FTI), but studies are just starting for preterm infants (PTI). The data also mostly come from western countries and little information is available for the Middle East. Here, we determined the composition and dynamics of the intestinal microbiota during the first month of life for PTI (n = 66) and FTI (n = 17) in Lebanon. Fecal samples were collected weekly and analyzed by quantitative PCR (q-PCR) and temporal temperature gradient gel electrophoresis (TTGE). We observed differences in the establishment and composition of the intestinal microbiota between the two groups. q-PCR showed that PTI were more highly colonized by Staphylococcus than FTI in the first three weeks of life; whereas FTI were more highly colonized by Clostridium clusters I and XI. At one month of life, PTI were mainly colonized by facultative anaerobes and a few strict anaerobes, such as Clostridium cluster I and Bifidobacterium. The type of feeding and antibiotic treatments significantly affected intestinal colonization. TTGE revealed low species diversity in both groups and high inter-individual variability in PTI. Our findings show that PTI had altered intestinal colonization with a higher occurrence of potential pathogens (Enterobacter, Clostridium sp) than FTI. This suggests the need for intervention strategies for PTI to modulate their intestinal microbiota and promote their health

Laboratory diagnosis of nonpolio enteroviruses: A review of the current literature

Infections by nonpolio enteroviruses (EVs) are highly prevalent, particularly among children and neonates, where they may cause substantial morbidity and mortality. Laboratory diagnosis of these viral infections is important in patient prognosis and guidance of clinical management. Although the laboratory diagnosis of nonpolio EVs is mainly based on molecular techniques, classical virus-isolation techniques are still used in reference laboratories. Other techniques, such as antigen detection and serology, are becoming obsolete and rarely used in diagnosis. An important part of diagnosis and surveillance of EV infections is viral typing by VP1 gene sequencing using conventional Sanger technique and more recently, full-genome next-generation sequencing. The latter allows the typing of all EVs, better investigation of EV outbreaks, detection of coinfection, and identification of severity markers in the EV genome