PURPOSE To evaluate the abilities of recombinant adenovirus carrying the basic fibroblast growth factor (bFGF) gene to (1) produce bFGF protein in vitro and (2) rescue retinal photoreceptors in Royal College of Surgeons (RCS) rats in vivo. METHODS Cultured human retinal pigment epithelial cells were infected with one of the following two replication-deficient adenoviral vectors that drive ins...

PURPOSE Transfer of growth-suppressive genes to lung tumors has therapeutic potential, but effective delivery techniques have not been developed. Here, we investigated gene delivery to lung tumors by aerosolization of adenoviral vectors incorporated into calcium phosphate precipitates. EXPERIMENTAL DESIGN To investigate the efficacy of this delivery method in normal and neoplastic lung, an ad...

OBJECTIVE To develop short hairpin RNA (shRNA) vectors and virions to trigger RNA interference against human p16. DESIGN AND INTERVENTIONS A modular vector-based shRNA system was used to construct multiple distinct shRNA vectors against the unique exon 1alphaof p16. Target sequences were designed using rigid criteria for length and GC content, along with basic local alignment search tool (BLA...

Previous work has implicated the cytokine leukemia inhibitory factor (LIF) in cutaneous inflammation, although results have differed as to whether LIF is pro- or anti-inflammatory in this setting. We examined edema, inflammatory cell infiltration, and cytokine responses following CFA injection in the adult mouse footpad. Inflammatory cell infiltration and edema are significantly enhanced when C...

As the limits of existing treatments for cancer are recognized, clearly novel therapies must be considered for successful treatment; cancer therapy using adenovirus vectors is a promising strategy. However tracking the biodistribution of adenovirus vectors in vivo is limited to invasive procedures such as biopsies, which are error prone, non-quantitative, and do not give a full representation o...

The regeneration of insulin-producing cells in vivo has emerged as a promising method for treating type I diabetes. Pancreatic duodenal homeobox-1 (Pdx-1), NeuroD, and Neurogenin-3 (Ngn3) are pancreatic transcription factors important for the development of insulin-producing cells in the liver. Other groups have demonstrated that adenoviral-mediated transgene expression of these transcription f...

Helper-dependent adenoviral vectors deleted of all viral coding sequences have shown an excellent gene expression profile in a variety of animal models, as well as a reduced toxicity after systemic delivery. What is still unclear is whether long-term expression and therapeutic dosages of these vectors can be obtained also in the presence of a preexisting immunity to adenovirus, a condition foun...

BACKGROUND Cell migration is a major contributor to injury-induced neointimal hyperplasia and depends on alteration of the proteolytic balance within the arterial wall toward matrix breakdown. This is partly mediated by the matrix metalloproteinases (MMPs) and their natural inhibitors, the tissue inhibitors of metalloproteinases (TIMPs). METHODS AND RESULTS An increase in expression of biolog...

Lung cancer is still a very severe disease which has a low survival rate due to local invasion and metastasis potentials in spite of many clinical challenges using anti-cancer drugs. Rho family small GTPases play pivotal roles in cell invasion and metastasis during carcinogenesis. In this study, we explored the inhibitory effect of adenoviral vector encoding dominant negative mutants of Rac, Rh...