Samuel Hellman — Page 2

PubMed2002

Transcriptional control of viral gene therapy by cisplatin.

Ionizing radiation (IR) and radical oxygen intermediates (ROIs) activate the early growth response-1 (Egr1) promoter through specific cis-acting sequences termed CArG elements. Ad.Egr.TNF.11D, a replication-deficient adenoviral vector containing CArG elements cloned upstream of the cDNA for human recombinant TNF-alpha was used to treat human esophageal adenocarcinoma and rat colon adenocarcinoma cells in culture and as xenografts in athymic nude mice. Cisplatin, a commonly used chemotherapeutic agent, causes tumor cell death by producing DNA damage and generating ROIs. The present studies demonstrate induction of TNF-alpha production in tumor cells and xenografts treated with the combination of Ad.Egr.TNF.11D and cisplatin. The results show that the Egr1 promoter is induced by cisplatin and that this induction is mediated in part through the CArG elements. These studies also demonstrate an enhanced antitumor response without an increase in toxicity following treatment with Ad.Egr.TNF.11D and cisplatin, compared with either agent alone. Chemo-inducible cancer gene therapy thus provides a means to control transgene expression while enhancing the effectiveness of commonly used chemotherapeutic agents.

Adenocarcinoma↗

PubMedDate not supplied

An evidence-based analysis of the management of localized prostate cancer.

PURPOSE: Patients with localized prostate cancer and their doctors face complex trade-offs when deciding on treatment. In this study, we modify the "number needed to treat" method to compare radical prostatectomy with radiotherapy. METHODS: A MEDLINE search was performed to identify all studies of radical protatectomy or radiotherapy for prostate cancer. Number needed to treat formulas were modified to account for not only survival but also for complications and their utilities. RESULTS: The unadjusted number needed to treat value for overall survival was 6 favoring prostatectomy (six patients have to undergo prostatectomy to have one more 10-year survivor than if they had undergone radiotherapy). Radiotherapy patients were 4 years older than prostatectomy patients. Because overall survival is strongly linked to patients' age and overall health, the numbers needed to treat for disease-specific and distant metastasis-free survival were analyzed to minimize patient selection bias. The unadjusted number needed to treat values for disease-specific and distant metastasis-free survival were 14 and 18, respectively. When number needed to treat is adjusted for complications and utilities, its value for overall survival is 14, disease-specific survival is -25, and distant metastasis free survival is -22, these last two favoring radiotherapy. CONCLUSIONS: Utility-adjusted numbers needed to treat for prostatectomy and radiotherapy are greatly influenced by the likelihood of complications and the utility loss ascribed to them. When literature-reported values are used, radiotherapy is superior, but the differences in outcomes are small. With prostate-specific antigen screening and refined treatment methods, these values will change, and the modified number needed to treat can be used to evaluate, report and compare results. The consequences of treatment in terms of both survival and quality of life determine patient choice and physician recommendations.

Aged↗