A molecular imaging system based on both transcriptional and genomic amplification to detect prostate cancer cells in vivo.

An imaging modality that can accurately discern prostate cancer (PCa) foci would be useful to detect PCa early or guide treatment. We have engineered numerous adenoviral vectors (Ads) to carry out reporter gene-based imaging using specific promoters to express a potent transcriptional activator, which in turn activates the reporter gene in PCa. This two-step transcriptional amplification (TSTA) method can boost promoters' activity, while maintaining cell specificity.

A hypoxia- and {alpha}-fetoprotein-dependent oncolytic adenovirus exhibits specific killing of hepatocellular carcinomas.

Purpose: Oncolytic adenoviruses (Ad) constitute a new promising modality of cancer gene therapy that displays improved efficacy over nonreplicating Ads. We have previously shown that an E1B 19-kDa-deleted oncolytic Ad exhibits a strong cell-killing effect but lacks tumor selectivity. To achieve hepatoma-restricted cytotoxicity and enhance replication of Ad within the context of tumor microenvironment, we used a modified human α-fetoprotein (hAFP) promoter to control the replication of Ad with a hypoxia response element (HRE).

A potent, imaging adenoviral vector driven by the cancer-selective mucin-1 promoter that targets breast cancer metastasis.

Purpose: With breast cancer, early detection and proper staging are critical, and will often influence both the treatment regimen and the therapeutic outcome for those affected with this disease. Improvements in these areas will play a profound role in reducing mortality from breast cancer.

Experimental Design: In this work we developed a breast cancer-targeted serotype 5 adenoviral vector, utilizing the tumor-specific mucin-1 promoter in combination with the two-step transcriptional amplification system, a system used to augment the activity of weak tissue-specific promoters.

Differential biodistribution of adenoviral vector in vivo as monitored by bioluminescence imaging and quantitative polymerase chain reaction.

A better understanding of the in vivo biodistribution of adenoviral vectors would enable the researcher to anticipate potential side effects due to off-targeted site of transduction, and aid in the strategic design of gene therapy. We combined real-time polymerase chain reaction with in vivo optical imaging to examine viral transduction in liver, lung, spleen, kidney, prostate, and lymph nodes. A replication-deficient serotype 5 adenoviral vector expressing the firefly luciferase gene under the control of a constitutive cytomegalovirus promoter was administered in vivo via different routes.

Characterization of the human glycerol kinase promoter: identification of a functional HNF-4alpha binding site and evidence for transcriptional activation.

Glycerol kinase (GK) is an enzyme at the interface of carbohydrate and fat metabolism. Mutations in the GK gene result in a rare inborn error of metabolism, GK deficiency (GKD), and at least one of these mutations (N288D) is associated with insulin resistance and diabetes mellitus. In an attempt to identify potential modifiers of the GKD phenotype, and to elucidate better the relationship between GKD and diabetes mellitus, we investigated the GK promoter.