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Old 05-03-2005, 12:46 PM   #1
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on today's medscape:Medscape

May 3, 2005

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Protozoan Protein Shows Antitumor Properties

NEW YORK (Reuters Health) May 02 - A protein from the intestinal protozoan Eimeria stimulates IL-12 release from dendritic cells and shows antitumor properties, according to a report from the May 1st issue of the International Journal of Cancer.

"While there is a lot to learn and much clinical work to be done, utilizing the organism's natural defenses will eventually provide the only sustainable therapy for (cancer and viral) diseases," Dr. David A. Juckett from Barros Research Institute, Holt, Michigan, told Reuters Health. This protein "offers a new, safe modulator of this system."

Dr. Juckett and colleagues isolated this protozoan protein from the bovine ileum and named barrogen.

Barrogen provided cure rates of 80% or greater when injected intraperitoneally in mice in the S-180 tumor model, the authors report. Combination of barrogen with GM-CSF resulted in survival of 100% in some experiments.

Barrogen treatment was associated with significant increases in IL-12, IL-6, TNF-alpha, and IFN-gamma, the report indicates. IL-12 levels were most affected, increasing five orders of magnitude after treatment with barrogen.

Barrogen also stimulated the release of dendritic cells from mouse spleens in vitro, the investigators report.

In further in vitro experiments, the researchers note, barrogen provided the stimulus for dendritic cell-dependent events leading to increased effector cell cytotoxicity.

Distribution of barrogen and barrogen-related activity along the bovine intestinal tract paralleled the natural resistance of these tissues to spontaneous tumorigenesis, the report indicates.

No toxicity was seen in preclinical studies at doses 1200 times higher than the therapeutic doses, the results indicate.

Barrogen is an "innate immune stimulator, which creates a programmed release of several cytokines and chemokines by providing a 'danger signal' detected by dendritic cells," Dr. Juckett explained. "Early evidence suggests that dendritic cells and their cytokine relea a central role in the activity of (barrogen).

"We have an ongoing phase I clinical trial and are planning a canine study in client-owned dogs with cancer," Dr. Juckett said. "From these studies we expect to learn more of the pharmacokinetics and pharmacodynamics in the clinical setting. We also anticipate obtaining an early indication of potential target tumors from these studies."

Int J Cancer 2005;114:756-765.
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