Background: Among the most prominent metabolic alterations in cancer cells are the increase in glucose consumption and the conversion of glucose to lactic acid via the reduction of pyruvate even in the presence of oxygen. This phenomenon, known as aerobic glycolysis or the Warburg effect, may provide a rationale for therapeutic strategies that inhibit tumour growth by administration of a ketogenic diet with average protein but low in carbohydrates and high in fat enriched with omega-3 fatty acids and medium-chain triglycerides (MCT).

The presented observations suggest a potential clinical relevance of IDO expression in DC-based therapeutic vaccines via the attraction or induction of FoxP3(+) T-cells.

Merkel cell carcinoma (MCC), an aggressive neuroendocrine skin tumor, is a polyomavirus‐induced human cancer. To study the causal relationship of MCC carcinogenesis with the integrated Merkel cell polyomavirus (MCPyV) in detail, well‐characterized MCC cell lines are needed. Consequently, in the current study, we established and characterized six MCPyV‐positive MCC cell lines. Microarray‐based comparative genomic hybridization revealed a stable genome carrying only a limited number of chromosomal gains and deletions. All cell lines expressed MCC markers Keratin‐20 and neuron‐specific enolase as well as truncated MCPyV‐encoded large T antigen (LT). For five cell lines, we were able to identify the MCPyV‐integration sites in introns of different genes. The LT‐truncating stop codon mutations and integration sites were affirmed in the respective clinical patient samples. Inverse PCR suggested that three of the cell lines contained MCPyV genomes as concatemers. This notion was confirmed for the two cell lines with known integration sites. Importantly, our observation of distinct stop codon mutations in cell lines with concatemeric MCPyV integration indicates that these LT‐truncating mutations occur before integration. In summary, we provide the detailed characterization of six MCPyV‐positive MCC cell lines, which are likely to serve as valuable tools in future MCC research.

Chorioamnionitis and funisitis are associated with neonatal morbidity and mortality. We hypothesized that chorioamnionitis may stress fetal endothelium, activate proinflammatory gene transcription. and affect angiogenic homeostasis in fetal capillaries. Placentas from preterm infants were stained for heat-shock protein 70, nuclear factor-B, hypoxia-inducible factor-1␣, and vascular endothelial growth factor (VEGF). VEGF receptors (VEGF-R) 1 and 2 as well as the receptor tyrosine kinase with immunoglobulin and epidermal growth factor homology domains (TIE-2), which is involved in vascular remodeling, were quantified. Immunohistochemistry was analyzed by counting positive capillaries in placental terminal villi. Staining intensity was quantified by a three-step semiquantitative scale. The samples were divided into three matched groups according to histology: chorioamnionitis with funisitis ("funisitis"), chorioamnionitis without funisitis ("chorioamnionitis"), and control group with no inflammation. In tissues from the funisitis or chorioamnionitis group, heat-shock protein 70 expression was increased over the control group. More nuclear factor-B-positive nuclei of endothelial cells in capillaries were counted in the funisitis and chorioamnionitis groups. Expression of VEGF and VEGF-R1 and -R2 were reduced in cases of funisitis or chorioamnionitis in comparison with controls. Hypoxia-inducible factor-1␣ expression tended to be slightly lower in the funisitis and chorioamnionitis groups but did not reach statistical significance. We speculate that cellular stress and changes in angiogenic homeostasis induced by proinflammatory activation of fetal endothelium in chorioamnionitis may not be limited to the placenta but may also involve other fetal organs. (Pediatr Res 58: 607-612, 2005) Abbreviations BPD, bronchopulmonary dysplasia CI, confidence interval HIF-1␣ hypoxia-inducible factor-1␣ HRP, horseradish peroxidase HSP70, heat-shock protein 70 IL, interleukin NF-B, nuclear factor-B TIE-2, tyrosine kinase with immunoglobulin and epidermal growth factor homology domains-2 VEGF, vascular endothelial growth factor VEGF-R, vascular endothelial growth factor receptor Chorioamnionitis is very common in preterm birth (1). Microbial infection of the amnion and chorion are detected in 60% of all preterm deliveries (2). Funisitis is diagnosed as an infiltration of neutrophils in the umbilical cord vessels (3) and can be considered as a progression of chorioamnionitis with systemic inflammatory response syndrome of the fetus (4). Although fetal inflammation reduces the incidence of respiratory distress syndrome (5,6) and increases the survival of preterm infants (7), the fetal inflammatory response has been associated with increased neonatal morbidity. The mechanisms by which fetal inflammation increases the incidence of bronchopulmonary dysplasia (BPD) (8), retinopathy of prematurity (9), intracranial hemorrhage (10), cerebral palsy, and adverse neurodevelopmental outcome (11-13) are not fully understood. Recently, a new poten...