Proapoptotic adenovirus vectors offer great promise for the treatment of @entity5 and nonmalignant conditions. @entity1067 ( @entity1067 ) is a common nonmalignant enlargement of the prostate that involves epithelial, stromal, and smooth muscle components of the gland. We tested the hypothesis that an adenovirus vector expressing Fas ligand can be used to induce apoptosis in the prostate. We analyzed the efficiency of transduction and apoptosis induction in primary cultures of @entity1 prostate cells after adenovirus-mediated gene transfer. Efficient transduction was observed in primary prostate epithelial cells. Stromal and smooth muscle cells were more difficult to transduce, as no coxsackie-adenovirus receptor (CAR) expression was detectable on these cells. However, transduction was achieved in these cells when the multiplicity of infection was increased to 100 focal-forming units per cell, or when the vectors were delivered as @entity78 precipitates. Infection of all three primary prostate cell types with an adenovirus vector that expresses Fas ligand (AdFasL/G) resulted in rapid apoptosis. Direct injection of the @entity35 prostate with an adenovirus vector carrying luciferase resulted in substantial luciferase expression. TUNEL analysis demonstrated that AdFasL/G administration induced low-level apoptosis in prostatic epithelial cells throughout the gland. As a first step toward enhancing the efficiency of prostate transduction in vivo, we tested an adenovirus vector that was engineered to have an expanded tropism. This vector, AdZ.F2K(pK7), was 10- to 500-fold more efficient than unmodified vectors in transducing prostate epithelial, smooth muscle, and stromal cells in culture. Moreover, AdZ.F2K(pK7) was more efficient than an unmodified vector at transducing the @entity35 prostate in vivo, although the effect was dose dependent.

Transduction and apoptosis induction in the XXXX prostate, using adenovirus vectors.

@entity1 :: ('9606', 'Species') :: ['human'] @entity5 :: ('MESH:D009369', 'Disease') :: ['cancer'] @entity1067 :: ('MESH:D011470', 'Disease') :: ['Benign prostate hyperplasia', 'BPH'] @entity78 :: ('MESH:C020243', 'Chemical') :: ['calcium phosphate'] @entity35 :: ('10116', 'Species') :: ['rat']
@entity35 :: (10116,Species) :: ['rat']
