and associated with changes in gene e pression that are apparent well before aneurysm formation is detected. Given the imple mentation of national screening programmes for AAA it is likely that in the future, diagnosis can be made much earlier in the natural history of the disease. Importantly, such patients www.selleckchem.com/products/Imatinib(STI571).html are those in whom medical therapy may be pertinent by way of preserving SMC in tegrity and function through targeting them to a repara tive phenotype. Conclusions Loss of arterial wall structure and integrity by impaired SMC function provides an e planation for the substan tial and progressive weakening of the aortic wall ob served in AAA.
In order to understand early changes in SMC behaviour, an e vivo model is appropriate and here we have shown that enzyme pre treatment of por cine carotid arteries maintained for 12 days within a bioreactor generates vessel wall disruption and SMC aberrancies comparable to those of end stage human tissue. Future studies with this engineered bioreactor will allow control of the physical environment e perienced by the cultured tissues and thus it holds significant potential for studying SMC dysfunction throughout early aneurysm development. Identifying key cellular and molecular mechanisms that promote SMC loss and aneurysm e pansion will inform new therapeutics to preserve SMC content and integrity in the aortic wall. Background The hallmark of po viruses utilization in anti cancer im munotherapy is their ability to e press large foreign genes without significant disruption of the viral genome.
This fea ture offers the possibility of e pressing comple eukaryotic sequences or multiple genes in permissive mammalian cells, ensuring correct post translational modifications. To date, different po viridae genera have been successfully used as tumor associated antigens vectors in e perimental models. Engineered attenuated recombinant vaccinia virus has now been widely employed as a cancer vaccine in a large number of clinical trials as well. The results of these trials demonstrated that recombinant vaccinia virus infection upon vaccination was safe and that a specific humoral or T cell response against the foreign inserted tumor associated antigen could be induced in several can cer patients. Vaccination with recombinant vaccinia virus can be achieved by systemic or intratumoral injection.
Recently, it was demonstrated that the antitumor activity induced by intratumoral vaccination with an avipo virus e pressing carcinoembryonic antigen and multiple co stimulatory molecules was superior to that induced by subcutaneous vaccination Batimastat in CEA transgenic mice. Similarly, we reported that the intramammary gland vaccin ation with the recombinant vaccinia virus neu vaccine was more effective than the subcutaneous vaccin ation in inhibiting mammary carcinogenesis in BALB neuT mice. In addition, the intramammary delivery was more effective than the subcutaneous vaccination in elicit ing anti Neu antibodies, selleck chem increasing anti Ne