Alleviating Cancer Drug Toxicity by Inhibiting a Bacterial Enzyme

The dose-limiting side effect of the common colon cancer chemotherapeutic CPT-11 is severe diarrhea caused by symbiotic bacterial β-glucuronidases that reactivate the drug in the gut. We sought to target these enzymes without killing the commensal bacteria essential for human health. Potent bacteria...

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Veröffentlicht in:	Science (American Association for the Advancement of Science) 2010-11, Vol.330 (6005), p.831-835
Hauptverfasser:	Wallace, Bret D, Wang, Hongwei, Lane, Kimberly T, Scott, John E, Orans, Jillian, Koo, Ja Seol, Venkatesh, Madhukumar, Jobin, Christian, Yeh, Li-An, Mani, Sridhar, Redinbo, Matthew R
Format:	Artikel
Sprache:	eng
Schlagworte:	60 APPLIED LIFE SCIENCES Anaerobic bacteria Anaerobic conditions Animals Antineoplastic agents Antineoplastic Agents, Phytogenic - metabolism Antineoplastic Agents, Phytogenic - toxicity BACTERIA Bacteria, Anaerobic - drug effects BASIC BIOLOGICAL SCIENCES Biological and medical sciences Camptothecin - analogs & derivatives Camptothecin - metabolism Camptothecin - toxicity Cancer Cell Line, Tumor Chemotherapy Colon - drug effects Colon - microbiology Colon - pathology Colorectal cancer CRYSTAL STRUCTURE Crystallography, X-Ray DIARRHEA Diarrhea - prevention & control Drug Evaluation, Preclinical Drug toxicity and drugs side effects treatment Drugs Enzyme Inhibitors - chemistry Enzyme Inhibitors - metabolism Enzyme Inhibitors - pharmacology ENZYMES Escherichia coli - enzymology Escherichia coli Proteins - antagonists & inhibitors Escherichia coli Proteins - chemistry Escherichia coli Proteins - isolation & purification Escherichia coli Proteins - metabolism Female Glucuronidase - antagonists & inhibitors Glucuronidase - chemistry Glucuronidase - isolation & purification Glucuronidase - metabolism Glucuronidase - pharmacology Humans Inhibitors Intestinal Mucosa - drug effects Intestinal Mucosa - microbiology Intestinal Mucosa - pathology LARGE INTESTINE Medical sciences MICE Mice, Inbred BALB C Microorganisms Models, Molecular Monomers NEOPLASMS ORAL ADMINISTRATION Pharmacology. Drug treatments Prodrugs - metabolism Prodrugs - toxicity Protein Conformation SIDE EFFECTS TARGETS TOXICITY Toxicity: digestive system
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