Prostate Cancer Scientific Abstracts - I

Welcome to the Prostate Cancer Guide scientific abstracts, author section I. Here you will find abstracts from the latest research being carried out in the field.

This section is recommended for people who have a scientific interest in prostate cancer. It is recommended that people without prior knowledge of prostate cancer visit the more general areas of the site (Prostate Cancer Guide).

Abstract Authors

 

Latest Prostate Cancer Abstract

Journal: Journal of the National Cancer Institute.

Issue: 2006, 98(9):625-36..

Pubmed ID: 16670388

Authors: Ito H, Aoki H, Kuhnel F, Kondo Y, Kubicka S, Wirth T, Iwado E, Iwamaru A, Fujiwara K, Hess KR, Lang FF, Sawaya R, Kondo S.

Title: Autophagic cell death of malignant glioma cells induced by a conditionally replicating adenovirus.

BACKGROUND: Conditionally replicating adenoviruses can be engineered to replicate selectively in cancer cells and cause cancer-specific cell lysis; thus they are considered a promising cancer therapy.

METHODS: To elucidate the mechanisms by which conditionally replicating adenoviruses induce cancer-specific cell death, we infected normal human fibroblasts (MRC5, telomerase negative), human malignant glioma (U373-MG and U87-MG), human cervical cancer (HeLa), and human prostate cancer (PC3) cells (all telomerase positive) with conditionally replicating adenoviruses regulated by the human telomerase reverse transcriptase promoter-Ad or control nonreplicating adenoviruses (Ad-GFP). Nonapoptotic autophagy was assessed in Ad-GFP- and human telomerase reverse transcriptase promoter-Ad-infected cells by examining cell morphology, the development of acidic vesicular organelles, and the conversion of microtubule-associated protein 1 light chain 3 from the cytoplasmic form to the autophagosome membrane form; signaling via mammalian target of rapamycin (mTOR), an autophagy-associated molecule, was monitored by western blot analysis. We also compared the growth of subcutaneous gliomas in nude mice that were treated by intratumoral injection with Ad-GFP or human telomerase reverse transcriptase promoter-Ad. Survival of athymic mice carrying intracranial gliomas treated by intratumoral injection with Ad-GFP or human telomerase reverse transcriptase promoter-Ad was compared by using the Kaplan-Meier method and the Cox-Mantel log-rank analysis. All statistical tests were two-sided.

RESULTS: hTERT-Ad induced tumor-specific autophagic cell death in tumor cells and in subcutaneous gliomas. human telomerase reverse transcriptase promoter-Ad-induced autophagy was associated with hTERT-Ad infection kinetics. The mTOR signaling pathway was suppressed in tumor cells and in subcutaneous gliomas treated with human telomerase reverse transcriptase promoter-Ad compared with GFP-Ad or no treatment as shown by reduced phosphorylation of mTOR's downstream target p70S6 kinase (p70S6K). human telomerase reverse transcriptase promoter-Ad treatment of mice (n = 7) slowed growth of subcutaneous gliomas (mean tumor volume = 39 mm3, 95% confidence interval [CI] = 23 to 54 mm3) compared with GFP-Ad treatment (n = 7) (mean tumor volume = 200 mm3, 95% CI = 149 to 251 mm3) at day 7 (volume difference = 161 mm3, 95% CI = 126 to 197 mm3; P < .001). Mice carrying intracranial tumors that were treated with three intratumoral injections of human telomerase reverse transcriptase promoter-Ad survived longer (53 days) than after treatment with GFP-Ad (29 days) (seven mice per group, difference = 24 days, 95% CI = 20 to 28 days; P < .001).

CONCLUSIONS: human telomerase reverse transcriptase promoter-Ad may kill telomerase-positive cancer cells by inducing autophagic cell death.

Contact: Department of Neurosurgery, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.