Assessing the potency of oral polio vaccine kept outside of the cold chain during a national immunization campaign in Chad.

This study is the first systematic documentation of the potency of monovalent oral polio vaccine type 3 (mOPV3) kept at ambient temperatures during a polio immunization campaign in Chad. During the study test vials were exposed to temperatures of up to 47.1 °C, and kept outside of the 2-8 °C range for a maximum of 86.9 hours. Post-campaign laboratory testing confirmed that the test vials were still potent, and in conformity with the defined release specifications. Further, the Vaccine Vial Monitors performed as expected, giving an early warning indication of when cumulative exposure to heat reached levels that may have negatively affected the vaccine's potency. This study provides proof-of-concept evidence that certain types of OPV remain potent and thus can be kept, for limited periods of time, as well as administered at ambient temperatures.

Up-regulation of vascular endothelial growth factor-A by active membrane-type 1 matrix metalloproteinase through activation of Src-tyrosine kinases.

Membrane-type 1 matrix metalloproteinase (MT1-MMP) and vascular endothelial growth factor (VEGF) are two key molecules involved in pericellular proteolysis and cell proliferation during tumor growth and angiogenesis. Our previous data showed that MT1-MMP overexpression in human breast carcinoma MCF7 cells induced an up-regulation of VEGF expression. This effect was associated in vivo with accelerated tumor growth and angiogenesis. We now provide evidence that MT1-MMP overexpression specifically affected VEGF-A production and failed to influence that of other VEGF family members (VEGF, B, C, D, or PlGF) or their receptors. The up-regulation of VEGF-A by MT1-MMP was related to an increased transcriptional activation rather than to a modification of mRNA stability. It was blocked by synthetic MMP inhibitors, TIMP2, but not TIMP-1 and abolished by a partial deletion of the catalytic domain or the cytoplasmic tail of MT1-MMP. Analysis of the signal transduction mechanisms demonstrated that MT1-MMP acts through a signaling pathway involving Src tyrosine kinases. Thus, our results provide new insight into the mechanisms of action of MT1-MMP during angiogenesis and suggest that the full enzymatic activity of MT1-MMP is required for a specific up-regulation of VEGF-A through an activation of Src tyrosine kinase pathways.