Palatal development of preterm and low birthweight infants compared to term infants – What do we know? Part 1: The palate of the term newborn

BACKGROUND: The evidence on prematurity as 'a priori' a risk for palatal disturbances that increase the need for orthodontic or orthognathic treatment is still weak. Further well-designed clinical studies are needed. The objective of this review is to provide a fundamental analysis of methodologies, confounding factors, and outcomes of studies on palatal development. One focus of this review is the analysis of studies on the palate of the term newborn, since knowing what is 'normal' is a precondition of being able to assess abnormalities. METHODS: A search profile based on Cochrane search strategies applied to 10 medical databases was used to identify existing studies. Articles, mainly those published before 1960, were identified from hand searches in textbooks, encyclopedias, reference lists and bibliographies. Sources in English, German, and French of more than a century were included. Data for term infants were recalculated if particular information about weight, length, or maturity was given. The extracted values, especially those from non-English paper sources, were provided unfiltered for comparison. RESULTS: The search strategy yielded 182 articles, of which 155 articles remained for final analysis. Morphology of the term newborn's palate was of great interest in the first half of the last century. Two general methodologies were used to assess palatal morphology: visual and metrical descriptions. Most of the studies on term infants suffer from lack of reliability tests. The groove system was recognized as the distinctive feature of the infant palate. The shape of the palate of the term infant may vary considerably, both visually and metrically. Gender, race, mode of delivery, and nasal deformities were identified as causes contributing to altered palatal morphology. Until today, anatomical features of the newborn's palate are subject to a non-uniform nomenclature. CONCLUSION: Today's knowledge of a newborn's 'normal' palatal morphology is based on non-standardized and limited methodologies for measuring a three-dimensional shape. This shortcoming increases bias and is the reason for contradictory research results, especially if pathologic conditions like syndromes or prematurity are involved. Adequate measurement techniques are needed and the 'normal palatal morphology' should be defined prior to new clinical studies on palatal development

Exosomal HIF1α supports invasive potential of nasopharyngeal carcinoma-associated LMP1-positive exosomes

It has emerged recently that exosomes are potential carriers of pro-tumorigenic factors that participate in oncogenesis. However, whether oncogenic transcription factors are transduced by exosomes is unknown. Hypoxia-inducible factor-1α (HIF1α) transcriptionally regulates numerous key aspects of tumor development and progression by promoting a more aggressive tumor phenotype, characterized by increased proliferation and invasiveness coupled with neoangiogenesis. It has been shown that the principal oncoprotein of Epstein-Barr virus (EBV), latent membrane protein 1 (LMP1), drives oncogenic processes and tumor progression of the highly invasive EBV malignancy, nasopharyngeal carcinoma (NPC). We now demonstrate that endogenous HIF1α is detectable in exosomes and that LMP1 significantly increases levels of HIF1α in exosomes. HIF1 recovered from exosomes retains DNA-binding activity and is transcriptionally active in recipient cells after exosome uptake. We also show that treatment of EBV-negative cells with LMP1-exosomes increases migration and invasiveness of NP cell lines in functional assays, which correlates with the phenotype associated with epithelial-mesenchymal transition (EMT). In addition, we provide evidence that HIF1α itself participates in exosome-mediated pro-metastatic effects in recipient cells, as exosome-mediated delivery of active and inactive forms of HIF1α results in reciprocal changes in the expression of E- and N-cadherins associated with EMT. Further, immunohistochemical analysis of NPC tumor tissues revealed direct correlation between protein levels of LMP1 and of the endosome/exosome marker tetraspanin, CD63, which suggests an increase in exosome formation in this EBV-positive malignancy. We hypothesize that exosome-mediated transfer of functional pro-metastatic factors by LMP1-positive NPC cells to surrounding tumor cells promotes cancer progression.Oncogene advance online publication, 24 March 2014; doi:10.1038/onc.2014.66

Personalized diagnosis and therapy.

Personalized medicine, i.e., the use of information about a person’s genes, proteins, metabolites, and environment to prevent, diagnose, and treat disease, has been much talked about in recent years. So some observers are wondering what the excitement is all about cumulating in the following statement: “Personalized health care is nothing new. Doctors have always tried to fit the therapy to the patient’s need if possible.” But what has happened more recently is that one has now begun to go a level deeper, i.e., to explore the biology of the disease and its treatment at the molecular level. However, molecular medicine does not per se define personalized medicine, but the molecular tools are important as they should enable greater relevance in the information provided by corresponding diagnostic tests (see below) (Edwards et al. 2008; Weedon et al. 2006; Romeo et al. 2007; Hegel et al. 1999; Wildin et al. 2001; Grant et al. 2006; Rothman and Greenland 2005; Raeder et al. 2006; Hegele et al. 2000; Capell and Collins 2006; Delepine et al. 2000; Janssens et al. 2006; Xiayan and Legido-Quigley 2008; Figeys and Pinto 2001; Müller 2002, 2010; Pearson et al. 2007; Janssens et al. 2008; Risch and Merikangas 1996; Janssens and van Duijn 2008; McCarthy 2003; McCarthy et al. 2003; Stumvoll et al. 2005; Lyssenko et al. 2005; Florez et al. 2003)