Verotoxin induces apoptosis and the complete, rapid, long-term elimination of human astrocytoma xenografts in nude mice.
Verotoxin 1 (VT1) is an E. coli elaborated subunit toxin active only against (tumor) cell lines that express the VT1 receptor, globotriaosyl ceramide-Gb3. Astrocytomas can be highly malignant brain tumors that remain refractory to clinical treatment. Some human astrocytoma cell lines are particularly sensitive to VT1 in vitro. To address whether this represents a feasible approach to the elimination of these tumors in man, human astrocytoma tumor xenografts in nude mice were treated with verotoxin. Following a single low-dose intratumoral injection of VT1, complete regression of a 1-cm-diameter tumor within 10 days was observed in all treated animals, without reoccurrence (up to 60 days). Apoptosis was demonstrated in both tumor and vascular cells within the treated xenograft. Verotoxin binding to tumor cells and blood vessels in sections of primary glioblastoma multiforme was found.
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Section of Infection, Immunity, Injury & Repair and Brain Tumor Research Laboratory, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada.
Rutka
J
J
Lingwood
C
C
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D001254:Astrocytoma / Q000098:blood supply / Q000188:drug therapy*; D001427:Bacterial Toxins / Q000494:pharmacology / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D003603:Cytotoxins / Q000494:pharmacology / Q000627:therapeutic use*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005909:Glioblastoma / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D022622:Shiga Toxin 1; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D001427:Bacterial Toxins; D003603:Cytotoxins; D022622:Shiga Toxin 1