Recombinant Lysyl Oxidase Propeptide Protein Inhibits Growth and Promotes Apoptosis of Pre-Existing Murine Breast Cancer Xenografts

Lysyl oxidase propeptide (LOX-PP) ectopic overexpression inhibits the growth of cancer xenografts. Here the ability and mode of action of purified recombinant LOX-PP (rLOX-PP) protein to inhibit the growth of pre-existing xenografts was determined. Experimental approaches employed were direct intratumoral injection (i.t.) of rLOX-PP protein into murine breast cancer NF639 xenografts, and application of a slow release formulation of rLOX-PP implanted adjacent to tumors in NCR nu/nu mice (n = 10). Tumors were monitored for growth, and after sacrifice were subjected to immunohistochemical and Western blot analyses for several markers of proliferation, apoptosis, and for rLOX-PP itself. Direct i.t. injection of rLOX-PP significantly reduced tumor volume on days 20, 22 and 25 and tumor weight at harvest on day 25 by 30% compared to control. Implantation of beads preloaded with 35 micrograms rLOX-PP (n = 10) in vivo reduced tumor volume and weight at sacrifice when compared to empty beads (p<0.05). A 30% reduction of tumor volume on days 22 and 25 (p<0.05) and final tumor weight on day 25 (p<0.05) were observed with a reduced tumor growth rate of 60% after implantation. rLOX-PP significantly reduced the expression of proliferation markers and Erk1/2 MAP kinase activation, while prominent increases in apoptosis markers were observed. rLOX-PP was detected by immunohistochemistry in harvested rLOX-PP tumors, but not in controls. Data provide pre-clinical findings that support proof of principle for the therapeutic anti-cancer potential of rLOX-PP protein formulations

From degeneration to infection/inflammation, and from individual-centered to ecologic approaches to investigation of evolving patterns of diseases occurrences in populations Da degeneração à infecção e da abordagem centrada no indivíduo à investigação ecológica dos padrões de ocorrência de enfermidades nas populações

Variation in attributes of CHD cases over time suggests a temporal change in the source sub-population of cases. It is proposed that an early 20th century expansion of a CHD-prone sub-population, characterized by high-serum cholesterol phenotype and high case-fatality - and which contributed with most of the CHD cases and deaths during the 1960s - may have followed the 1918 Influenza Pandemic. The extinction of those birth-cohorts would have resulted in a relative increase in cases coming from a second source sub-population, characterized by insulin resistance and chronic expression of low grade inflammation markers, comparatively less vulnerable to acutely die from CHD. This re-interpretation of the CHD trend, and the abandonment of the idea of degeneration for inflammation/infection calls for a change in epidemiology. Besides exposures (diet, infection...), temporal variations in proportional representations of inherited and acquired phenotypes associated with individual resistance/vulnerability, would be important determinants of evolving patterns of diseases occurrences in populations.<br>A variação registrada nos atributos dos casos de Doença Isquêmica do Coração (DIC) ao longo do tempo sugere variação temporal na subpopulação fonte dos casos. Propõe-se que tenha ocorrido, em associação com a Pandemia de Influenza de 1918, a expansão de uma subpopulação caracterizada por um fenótipo de hipercolesterolemia e alta propensão à mortalidade por DIC, que teria contribuído com a maior parte dos casos e dos óbitos por DIC registrados na década de 1960. A progressiva extinção daquelas coortes de nascimento teria resultado em crescimento relativo dos casos de DIC oriundos de uma segunda subpopulação, caracterizada por resistência à insulina e expressão de marcadores associados a inflamação crônica subclínica. Esta re-interpretação da tendência temporal da mortalidade por DIC, e o abandono da idéia de degeneração pela idéia de inflamação/infecção pede por uma mudança na epidemiologia. Além de exposições ambientais (dieta, infecção), variações temporais nas representações proporcionais de fenótipos associados à resistência e à vulnerabilidade individual seriam importantes determinantes dos padrões de ocorrência de doenças em populações

Correlation analysis of alveolar bone loss in buccal/palatal and proximal surfaces in rats

The aim was to correlate alveolar bone loss in the buccal/palatal and the mesial/distal surfaces of upper molars in rats. Thirty-three, 60-day-old, male Wistar rats were divided in two groups, one treated with alcohol and the other not treated with alcohol. All rats received silk ligatures on the right upper second molars for 4 weeks. The rats were then euthanized and their maxillae were split and defleshed with sodium hypochlorite (9%). The cemento-enamel junction (CEJ) was stained with 1% methylene blue and the alveolar bone loss in the buccal/palatal surfaces was measured linearly in 5 points on standardized digital photographs. Measurement of the proximal sites was performed by sectioning the hemimaxillae, restaining the CEJ and measuring the alveolar bone loss linearly in 3 points. A calibrated and blinded examiner performed all the measurements. Intraclass Correlation Coefficient revealed values of 0.96 and 0.89 for buccal/lingual and proximal surfaces, respectively. The Pearson Correlation Coefficient (r) between measurements in buccal/palatal and proximal surfaces was 0.35 and 0.05 for the group treated with alcohol, with and without ligatures, respectively. The best correlations between buccal/palatal and proximal surfaces were observed in animals not treated with alcohol, in sites both with and without ligatures (r = 0.59 and 0.65, respectively). A positive correlation was found between alveolar bone loss in buccal/palatal and proximal surfaces. The correlation is stronger in animals that were not treated with alcohol, in sites without ligatures. Areas with and without ligature-induced periodontal destruction allow detection of alveolar bone loss in buccal/palatal and proximal surfaces