GM3 as a novel growth regulator for human gliomas.
The simple ganglioside GM3 inhibits proliferation and induces apoptosis in proliferating immature rodent CNS cells. To determine whether GM3 influenced the expansion of human neural tumors the effects of GM3 treatment on primary human brain tumors were assayed. Here we demonstrate that GM3 treatment dramatically reduces cell numbers in primary cultures of high-grade human glioblastoma multiforme (GBM) tumors and the rat 9L cell gliosarcoma cell line. By contrast, GM3 treatment had little effect on cell number in cultures of normal human brain. A single injection of GM3 3 days after intracranial implantation of 9L tumor cells in a murine xenograft model system resulted in a significant increase in the symptom-free survival period of host animals. The effects of GM3 were not restricted to GBMs and 9L cells. Cultures of high-grade ependymomas, mixed gliomas, astrocytomas, oligodendrogliomas, and gangliogliomas were all susceptible to GM3 treatment. These results suggest that GM3 may have considerable value as a selectively toxic chemotherapeutic agent for human high-grade gliomas.
The Neurosurgical Laboratories of Brigham and Women's Hospital, The Children's Hospital, The Dana Farber Cancer Institute, 75 Francis Street, Boston, Massachusetts 02115, USA.
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EN
Noll
J
J
Lin
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Y
Nakatsuji
R H
RH
Miller
P M
PM
Black
D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002675:Child, Preschool; D004354:Drug Screening Assays, Antitumor; D005679:G(M3) Ganglioside / Q000494:pharmacology / Q000627:therapeutic use*; D005909:Glioblastoma / Q000188:drug therapy / Q000473:pathology; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D051381:Rats; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000502:physiology
D005679:G(M3) Ganglioside