Prognostic value of cytokinetic parameters in lung cancer after in vivo bromodeoxyuridine labelling.

Department of Molecular Cell Biology and Genetics, University of Maastricht, The Netherlands. BACKGROUND: To improve the overall survival rate in lung cancer by adjustment of treatment protocols on basis of tumour characteristics of individual patients, independent predictive parameters are required. Therefore, we evaluated the prognostic value of cytokinetic parameters such as bromodeoxyuridine (BrdU) labelling index (LI), S-phase fraction (SPF), unlabelled S-phase fraction (USPF), S-phase duration (Ts) and potential tumour doubling time (Tpot), next to more established parameters. MATERIALS AND METHODS: To this end a series of 92 bronchoscopic specimens of in vivo BrdU labelled lung cancer patients, 72 presenting with non-small cell lung carcinoma (NSCLC) and 20 patients with small cell lung carcinoma (SCLC), were analysed flow cytometrically. Clinical as well as cytokinetic data were collected and related to survival times over a follow-up period of 2 to 7 years. RESULTS: We found that Tpot was a significant independent discriminator of good and poor prognosis in NSCLC. In particular, in non-squamous NSCLC a short Tpot, short Ts and high LI predicted for shorter survival time. In squamous cell carcinoma, a high USPF may predict a shorter survival period, although the correlation was only borderline-significant. CONCLUSIONS: We conclude that these parameters may in future be of use in drawing up more adequate treatment schedules for individual lung cancer patients

Time course of atrial fibrillation-induced cellular structural remodeling in atria of the goat.

Background: Previously we documented cellular structural changes of a non-degenerative nature in atrial myocytes after atrial fibrillation (AF) in the goat. The time course of these changes was not studied. Methods and Results: Cellular structural changes were studied by light- and electron microscopy and immunohistochemistry in goat atria after 0-16 weeks AF. The first sign of cellular structural remodeling was a more homogeneous chromatin distribution, at 1 week of AF. Sub-structural changes in mitochondria and sarcoplasmic reticulum occurred gradually. Cellular degeneration was absent. The degree of myolysis and glycogen accumulation increased till 8 weeks of AF and did not increase further from thereon. After 16 weeks of AF, 42% of the myocytes in the right atrial free wall were affected by myolysis. The diameter of the atrial myocytes increased. Dedifferentiation of the atrial myocytes was suggested by altered expression patterns of structural proteins, such as the disappearance of cardiotin (1 week), the A-I junctional part of titin (4 weeks), desmin at the intercalated disk (ID) (8 weeks) and a gradual re-expression of alpha-smooth muscle actin. Conclusion: Remodeling of the cellular ultrastructure in atrial myocardium of the goat develops progressively during AF. Re-expression of fetal proteins indicate dedifferentiation of atrial myocytes, analogous to observations in hibernating myocardium of the ventricle