RESUMO
Systemic delivery of oncolytic and immunomodulatory adenoviruses may be required for optimal effects on human malignancies. Mesenchymal stromal cells (MSCs) can serve as delivery systems for cancer therapeutics due to their ability to transport and shield these agents while homing to tumors. We now use MSCs to deliver a clinically validated binary oncolytic and helper-dependent adenovirus combination (CAdVEC) to tumor cells. We show successful oncolysis and helper-dependent virus function in tumor cells even in the presence of plasma from adenovirus-seropositive donors. In both two- and three-dimensional cultures, CAdVEC function is eliminated even at high dilutions of seropositive plasma but is well sustained when CAdVEC is delivered by MSCs. These results provide a robust in vitro model to measure oncolytic and helper-dependent virus spread and demonstrate a beneficial role of using MSCs for systemic delivery of CAdVEC even in the presence of a neutralizing humoral response.
RESUMO
BACKGROUND: The proper head positioning decreases the surgical complications by enabling a better surgical maneuverability. Middle cerebral artery (MCA) bifurcation aneurysms have been classified by Dashti et al. [Surg Neurol. 2007 May;67(5):441-56] as the intertruncal, inferior, lateral, insular, and complex types based on dome projection. Our aim was to identify the optimum head positions and to explain the anatomic variables, which may affect the surgical strategy of MCA bifurcation aneurysms. METHODS: The lateral supraorbital approach bilaterally was performed in the 4 cadaveric heads. All steps of the dissection were recorded using digital camera. RESULTS: The distal Sylvian fissure (SF) dissection may be preferred for insular type and the proximal SF dissection may be preferred for all other types. Fifteen degrees head rotation was found as the most suitable position for the intertruncal, lateral type and subtype of complex aneurysms related with superior trunk. Thirty degrees head rotation was found the most suitable position for the inferior type, insular type, and subtype of complex aneurysms related with inferior trunk. CONCLUSIONS: The head positioning in middle cerebral bifurcation aneurysms surgery is a critical step. It should be tailored according to the projection and its relationship with the parent vessels of the middle cerebral bifurcation.
