Abrogation of Junctional Adhesion Molecule-A Expression Induces Cell Apoptosis and Reduces Breast Cancer Progression

Intercellular junctions promote homotypic cell to cell adhesion and transfer intracellular signals which control cell growth and apoptosis. Junctional adhesion molecule-A (JAM-A) is a transmembrane immunoglobulin located at tight junctions of normal epithelial cells of mammary ducts and glands. In the present paper we show that JAM-A acts as a survival factor for mammary carcinoma cells. JAM-A null mice expressing Polyoma Middle T under MMTV promoter develop significantly smaller mammary tumors than JAM-A positive mice. Angiogenesis and inflammatory or immune infiltrate were not statistically modified in absence of JAM-A but tumor cell apoptosis was significantly increased. Tumor cells isolated from JAM-A null mice or 4T1 cells incubated with JAM-A blocking antibodies showed reduced growth and increased apoptosis which paralleled altered junctional architecture and adhesive function. In a breast cancer clinical data set, tissue microarray data show that JAM-A expression correlates with poor prognosis. Gene expression analysis of mouse tumor samples showed a correlation between genes enriched in human G3 tumors and genes over expressed in JAM-A +/+ mammary tumors. Conversely, genes enriched in G1 human tumors correlate with genes overexpressed in JAM-A−/− tumors. We conclude that down regulation of JAM-A reduces tumor aggressive behavior by increasing cell susceptibility to apoptosis. JAM-A may be considered a negative prognostic factor and a potential therapeutic target

Efficiency of Class I and Class II malocclusion treatment with four premolar extractions

Four premolar extractions is a successful protocol to treat Class I malocclusion, but it is a less efficient way when compared with other Class II treatment protocols. Objective: The objective of this study was to evaluate the influence of anteroposterior discrepancy on the success of four premolar extractions protocol. For that, treatment efficiency of Class I and complete Class II malocclusions, treated with four premolar extractions were compared. Methods: A sample of 107 records from 75 Class I (mean age of 13.98 years - group 1) and 32 Class II (mean age of 13.19 years - group 2) malocclusion patients treated with four premolar extractions was selected. The initial and final occlusal status of each patient was evaluated on dental casts with the PAR index. The treatment time was calculated based on the clinical charts, and the treatment efficiency was obtained by the ratio between the percentage of PAR reduction and treatment time. The PAR index and its components, the treatment time and the treatment efficiency of the groups were statistically compared with t tests and Mann-Whitney U-test. Results: The Class II malocclusion patients had a greater final PAR index than Class I malocclusion patients, and similar duration (Class I - 28.95 mo. and Class II - 28.10 mo.) and treatment efficiency. Conclusion: The treatment of the complete Class II malocclusion with four premolar extractions presented worse occlusal results than Class I malocclusion owing to incomplete molar relationship correction