High threshold of β1 integrin inhibition required to block collagen I-induced membrane type-1 matrix metalloproteinase (MT1-MMP) activation of matrix metalloproteinase 2 (MMP-2).

Background: Matrix metalloproteinase-2 (MMP-2) is an endopeptidase that facilitates extracellular matrix remodeling and molecular regulation, and is implicated in tumor metastasis. Type I collagen (Col I) regulates the activation of MMP-2 through both transcriptional and post-transcriptional means; however gaps remain in our understanding of the involvement of collagen-binding β1 integrins in collagen-stimulated MMP-2 activation.

Methods: Three β1 integrin siRNAs were used to elucidate the involvement of β1 integrins in the Col I-induced MMP-2 activation mechanism.

The type I collagen induction of MT1-MMP-mediated MMP-2 activation is repressed by alphaVbeta3 integrin in human breast cancer cells.

The influence of alphaVbeta3 integrin on MT1-MMP functionality was studied in human breast cancer cells of differing beta3 integrin status. Overexpression of beta3 integrin caused increased cell surface expression of alphaV integrin and increased cellular adhesion to extracellular matrix (ECM) substrates in BT-549, MDA-MB-231 and MCF-7 cells. beta3 integrin expression also enhanced the migration of breast cancer cells on ECM substrates and enhanced collagen gel contraction.

Effect of salbutamol on oxygen saturation in COPD.

The effect of nebulized salbutamol on oxygen saturation in COPD was evaluated in this study. Twenty patients aged 56-75 years with stable COPD were recruited to the study. All patients received 5 mg of salbutamol nebulizer driven by oxygen at 8 L/min.

Is driving oxygen flow rate clinically important for nebulizer therapy in patients with COPD?

Our study suggests that the administration of bronchodilator drug via nebulizer powered by flow rate 6 L/min is more suitable in COPD patients. The oxygen flow rates should not be given more than 6 L/min. In this study, we recruited COPD patients in a stable stage, in whom the risk of hyperoxic induced hypercarbia is less than in the acute exacerbation stage.