Prognostic value of matrix metalloproteinases in oral squamous cell carcinoma.

The aim of this study was to investigate whether there is a correlation between the expressions of four matrix metalloproteinases (MMPs): MMP-2, MMP-7, MMP-9 and MMP-13, and the TNM (tumour-node-metastasis) stages of oral squamous cell carcinoma (OSCC); and to explore the implication of these MMPs in OSCC dissemination. Samples from 61 patients diagnosed with oropharyngeal tumour were studied by immunohistochemistry against MMP-2, MMP-7, MMP-9 and MMP-13. The assessment of immunoreactivity was semi-quantitative. The results showed that MMP-2 and MMP-9 had similar expression patterns in the tumour cells with no changes in the immunoreactivity during tumour progression. MMP-9 always had the highest expression, whereas that of MMP-2 was moderate. MMP-7 showed a significant decrease in expression levels during tumour evolution. MMP-13 had constant expression levels within stage T2 and T3, but showed a remarkable decline in immunoreactivity in stage T4. No significant differences in the MMPs immunoreactivity between tumour cells and stroma were observed. Although strong evidence for the application of MMPs as reliable predictive markers for node metastasis was not acquired, we believe that combining patients' MMPs expression intensity and clinical features may improve the diagnosis and prognosis. Strong evidence for the application of MMPs as reliable predictive markers for node metastasis was not acquired. Application of MMPs as prognostic indicators for the malignancy potential of OSCC might be considered in every case of tumour examination. We believe that combining patients' MMPs expression intensity and clinical features may improve the process of making diagnosis and prognosis.

A hypoxia complement differentiates the muscle response to endurance exercise.

Metabolic stress is believed to constitute an important signal for training-induced adjustments of gene expression and oxidative capacity in skeletal muscle. We hypothesized that the effects of endurance training on expression of muscle-relevant transcripts and ultrastructure would be specifically modified by a hypoxia complement during exercise due to enhanced glycolytic strain. Endurance training of untrained male subjects in conditions of hypoxia increased subsarcolemmal mitochondrial density in the recruited vastus lateralis muscle and power output in hypoxia more than training in normoxia, i.e. 169 versus 91% and 10 versus 6%, respectively, and tended to differentially elevate sarcoplasmic volume density (42 versus 20%, P = 0.07). The hypoxia-specific ultrastructural adjustments with training corresponded to differential regulation of the muscle transcriptome by single and repeated exercise between both oxygenation conditions. Fine-tuning by exercise in hypoxia comprised gene ontologies connected to energy provision by glycolysis and fat metabolism in mitochondria, remodelling of capillaries and the extracellular matrix, and cell cycle regulation, but not fibre structure. In the untrained state, the transcriptome response during the first 24 h of recovery from a single exercise bout correlated positively with changes in arterial oxygen saturation during exercise and negatively with blood lactate. This correspondence was inverted in the trained state. The observations highlight that the expression response of myocellular energy pathways to endurance work is graded with regard to metabolic stress and the training state. The exposed mechanistic relationship implies that the altitude specificity of improvements in aerobic performance with a 'living low-training high' regime has a myocellular basis.

Assessment of air space size characteristics by intercept (chord) measurement: an accurate and efficient stereological approach.

The mean linear intercept (chord) length (L(m)) is a useful parameter of peripheral lung structure as it describes the mean free distance in the air spaces. It is often misinterpreted as a measure of "alveolar size," and its estimation is fraught with a number of pitfalls. We present two methods for the accurate estimation of L(m): 1) the indirect method, which derives L(m) from the volume-to-surface ratio of air spaces estimated by point counting methods, and 2) the direct method, which uses a set of random intercepts and calculates L(m) from their frequency distribution, for which we introduce a new and accurate method. Both methods are efficient and, with proper precautions, unbiased. The meaning of L(m) is assessed in two different examples. In a physiological study, the effect of different inflation levels is studied, showing that L(m) critically depends on lung inflation. In an experimental study on emphysema-like changes in a genetic mouse model, the effect of heterogeneity of air space size is assessed; these results are obtained partly because of differences in lung volume due to altered recoil in the emphysematous lungs. In conclusion, although L(m) is not a robust parameter of internal lung structure because it crucially depends on lung volume, it is still a valid measure for which accurate and efficient methods are available that yield additional parameters such as size distribution or alveolar surface area.