Synergistic effect of targeting the epidermal growth factor receptor and hyaluronan synthesis in oesophageal squamous cell carcinoma cells.

BACKGROUND AND PURPOSE: Worldwide, oesophageal cancer is the eighth most common cancer and has a very poor survival rate. In order to identify new tolerable treatment options for oesophageal squamous cell carcinoma (ESCC), erlotinib was tested with moderate efficacy in phase I and II studies. As 4-methylumbelliferone (4-MU), an hyaluronan (HA) synthesis inhibitor showed anti-cancer effects in vitro, and in ESCC xenograft tumours, we investigated whether the anti-cancer effects of erlotinib could be augmented by combining it with 4-MU. EXPERIMENTAL APPROACH: ESCC cell lines were treated with erlotinib or gefitinib (1 µmol·L-1 ) and 4-MU (300 µmol·L-1 ), and the cell count, cell cycle progression and migration were determined as compared to the single agents and the solvent-control. KEY RESULTS: The combination of erlotinib and 4-MU synergistically inhibited the proliferation of ESCC cell lines. Furthermore, the migration speed of ESCC cell line KYSE-410 in gap closure assays was significantly reduced by the combination of erlotinib and 4-MU. Decreased ERK phosphorylation could explain the anti-proliferative and anti-migratory effects in the combined treatment group. Finally, the combination was additionally able to decrease the growth of multicellular tumour spheroids, a three-dimensional cell culture model that was associated with sustained inhibition of ERK1/2 phosphorylation. CONCLUSIONS AND IMPLICATIONS: The combination of 4-MU and erlotinib showed promising anti-cancer efficacies in the ESCC cell lines.

Malocclusion and the need for orthodontic treatment in 9-year-old children. Survey based on the Swedish National Board of Health and Welfare Scale.

In this study the prevalence of malocclusion and the need for orthodontic treatment was studied in 1,020 children (541 boys and 479 girls). At the time of examination they were between the ages of 8 years 5 months and 9 years 5 months. The frequency of dental, space and occlusion anomalies was recorded and compared with those in other studies. The need for orthodontic treatment was judged according to the 5-point scale of the Swedish National Board of Health and Welfare (1996). In 32% of the children there was an urgent need for treatment (Grade 3 and 4) in a further 32% treatment would be desirable (Grade 2). There was a little need for treatment (Grade 1) in 24% and no need (Grade 0) in 12%.

Synthetic gestagens exert differential effects on arterial thrombosis and aortic gene expression in ovariectomized apolipoprotein E-deficient mice.

BACKGROUND AND PURPOSE: Combined hormone replacement therapy with oestrogens plus the synthetic progestin medroxyprogesterone acetate (MPA) is associated with an increased risk of thrombosis. However, the mechanisms of this pro-thrombotic effect are largely unknown. The purpose of this study was to: (i) compare the pro-thrombotic effect of MPA with another synthetic progestin, norethisterone acetate (NET-A), (ii) determine if MPA's pro-thrombotic effect can be antagonized by the progesterone and glucocorticoid receptor antagonist mifepristone and (iii) elucidate underlying mechanisms by comparing aortic gene expression after chronic MPA with that after NET-A treatment. EXPERIMENTAL APPROACH: Female apolipoprotein E-deficient mice were ovariectomized and treated with placebo, MPA, a combination of MPA + mifepristone or NET-A for 90 days on a Western-type diet. Arterial thrombosis was measured in vivo in a photothrombosis model. Aortic gene expression was analysed using microarrays; GeneOntology and KEGG pathway analyses were conducted. KEY RESULTS: MPA's pro-thrombotic effects were prevented by mifepristone, while NET-A did not affect arterial thrombosis. Aortic gene expression analysis showed, for the first time, that gestagens induce similar effects on a set of genes potentially promoting thrombosis. However, in NET-A-treated mice other genes with potentially anti-thrombotic effects were also affected, which might counterbalance the effects of the pro-thrombotic genes. CONCLUSIONS AND IMPLICATIONS: The pro-thrombotic effects of synthetic progestins appear to be compound-specific, rather than representing a class effect of gestagens. Furthermore, the different thrombotic responses elicited by MPA and NET-A might be attributed to a more balanced, 'homeostatic' gene expression induced in NET-A- as compared with MPA-treated mice.

Reliability of electromagnetic articulography recording during speaking sequences.

For the development of malocclusions and speech disorders, major aetiological significance is attributed to orofacial malfunctions, especially of the tongue. The position of the tongue to the alveolar arch and teeth, particularly within the area of the tip of the tongue, is of special interest for orthodontists. Electromagnetic articulography is a new technique used to examine tongue function and to record its movement in the midsagittal plane. The aim of the study was to determine whether this procedure offers suitable and reliable results. Thirty-one subjects aged 14.3-37.3 years had to repeat speaking sequences five times. The German syllables they had to repeat were /asa/, /ascha/, /ata/, /ala/, /ana/, /aka/. The tongue movements were registered with an 'Articulograph AG 100'. Distances, angles and encircled planes were evaluated, and the proportion of intra-individual to overall variability was calculated in order to check the reliability of the courses of movement. Angles and distances especially showed, depending on the position of the receiver coils, strong reliability during speaking sequences, whereas area produced unfavourable results. The analysis of long trajectories and angles appeared favourable in order to describe the courses of movement. This required, however, a systematic assessment of functional movement with electromagnetic articulography.