Tumor necrosis factor-related apoptosis-inducing ligand: A novel mechanism for Bacillus Calmette-Guerin-induced antitumor activity

Aaron T LUDWIG; Jill M MOORE; Yi  Luo; Xiaohong Chen; Nicole A SALTSGAVER; Michael A O'DONNELL; Thomas S GRIFFITH

doi:10.1158/0008-5472.CAN-04-0374

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Tumor necrosis factor-related apoptosis-inducing ligand: A novel mechanism for Bacillus Calmette-Guerin-induced antitumor activity

Journal article

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Tumor necrosis factor-related apoptosis-inducing ligand: A novel mechanism for Bacillus Calmette-Guerin-induced antitumor activity

Aaron T LUDWIG, Jill M MOORE, Yi Luo, Xiaohong Chen, Nicole A SALTSGAVER, Michael A O'DONNELL and Thomas S GRIFFITH

Cancer research (Chicago, Ill.), Vol.64(10), pp.3386-3390

2004

DOI: 10.1158/0008-5472.CAN-04-0374

PMID: 15150089

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Abstract

Mycobacterium bovis Bacillus Calmette-Guérin (BCG) use in the treatment of bladder cancer was first reported in 1976, but the mechanism of the induced antitumor activity has still not been fully explained. BCG is a potent immunostimulant, normally producing a Th1 cytokine response, including IFN. Recent studies have shown CpG oligodeoxynucleotide induce tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) expression via IFN production. Given that Mycobacterial DNA contains high amounts of CpG motifs, we hypothesized that BCG’s antitumor properties are akin to CpG oligodeoxynucleotide, where the cytokine response to BCG induces TRAIL up-regulation. Using ELISA, urine IFN-γ, and TRAIL levels were initially undetectable in BCG therapy patients but were high after later induction treatments. More importantly, patients that responded to BCG therapy had significantly higher urine TRAIL levels, which killed bladder tumor cells in vitro versus nonresponders. Flow cytometry of fresh urine revealed TRAIL-expressing neutrophils. Given these data, we propose TRAIL plays a role in BCG-induced antitumor effects.

Antineoplastic Agents

Tumors

Biological and medical sciences

Medical sciences

Pharmacology. Drug treatments

Details

Title: Subtitle: Tumor necrosis factor-related apoptosis-inducing ligand: A novel mechanism for Bacillus Calmette-Guerin-induced antitumor activity
Creators: Aaron T LUDWIG - Department of Urology, University of Iowa, Iowa City, Iowa, United States
Jill M MOORE - Department of Urology, University of Iowa, Iowa City, Iowa, United States
Yi Luo - Department of Urology, University of Iowa, Iowa City, Iowa, United States
Xiaohong Chen - Department of Urology, University of Iowa, Iowa City, Iowa, United States
Nicole A SALTSGAVER - Department of Urology, University of Iowa, Iowa City, Iowa, United States
Michael A O'DONNELL - Department of Urology, University of Iowa, Iowa City, Iowa, United States
Thomas S GRIFFITH - Department of Urology, University of Iowa, Iowa City, Iowa, United States
Resource Type: Journal article
Publication Details: Cancer research (Chicago, Ill.), Vol.64(10), pp.3386-3390
Publisher: American Association for Cancer Research; Philadelphia, PA
DOI: 10.1158/0008-5472.CAN-04-0374
PMID: 15150089
ISSN: 0008-5472
eISSN: 1538-7445
Language: English
Date published: 2004
Academic Unit: Urology
Record Identifier: 9984051797002771

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