Abstract: A conditionally replicating adenovirus were generated that can specifically replicate and express therapeutic genes in neuroendocrine tumors. The promoter-specific expression of the adenoviruses is regulated upstream by an INSM1 (insulinoma-associated-1) promoter that is silent in normal adult tissues but active in developing neuroendocrine cells and neuroendocrine tumors. By placing the I NSM 1-promoter with an insulator and two copies of neuronal restrictive silencer elements in an adenoviral vector, the construct can retain tumor specificity and drive expression of a mutated adenovirus E1A gene (?24E1A) and the herpes simplex virus thymidine kinase gene. The I NSM1-promoter-driven viruses could replicate specifically in the I NSM1-positive cells and I NSM1-specific HSV-tk expression in combination with ganciclovir treatment displayed dose-dependent tumor cell-specific killing in insulinomas.

Abstract: A conditionally replicating adenovirus were generated that can specifically replicate and express therapeutic genes in neuroendocrine tumors. The promoter-specific expression of the adenoviruses is regulated upstream by an INSM1 (insulinoma-associated-1) promoter that is silent in normal adult tissues but active in developing neuroendocrine cells and neuroendocrine tumors. By placing the INSM1-promoter with an insulator and two copies of neuronal restrictive silencer elements in an adenoviral vector, the construct can retain tumor specificity and drive expression of a mutated adenovirus E1A gene (424E1A) and the herpes simplex virus thymidine kinase gene. The INSM1-promoter-driven viruses could replicate specifically in the INSM1-positive cells and I NSM1-specific HSV-tk expression in combination with ganciclovir treatment displayed dose-dependent tumor cell-specific killing in insulinomas.

Abstract: An apparatus and a method for aligning the loading/unloading of a wafer cassette to/from a loadport by an overhead hoist transport system are described. The apparatus utilizes a loadport that is equipped with at least two spaced-apart laser beam projectors mounted on a top surface of the loadport for projecting laser beams into a CCD array mounted on the bottom surface of the OHT rail facing the loadport. The actual position of the loadport can thus be continuously monitored and determined, and any necessary adjustment in positions of the OHT delivery arm for the wafer cassette can be made. A process controller is further provided for receiving the signal from the CCD array, or any other energy receiving means and for comparing to pre-stored data for sending a control signal to the OHT delivery arm.