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[Antitumor efficacy of recombinant interferon-beta on human glioma]
Abstract:
The antitumor efficacy of recombinant interferon-beta (rIFN-beta) on human glioblastomas was investigated in vitro and in meningeal gliomatosis(MG) models. A total of 1.5 X 10(5) human glioma (ONS-12 and ONS-20) cells were suspended in 2 ml of RPMI-1640 with 10% fetal calf serum and placed in plastic dishes (Falcon #3001). rIFN-beta 10(2)-10(5) units were then added to each culture dish on days 3, 5 and 7. Both ONS-12 and ONS-20 human glioma cells were suppressed with a low dose of rIFN-beta. As MG models, 5 X 10(7) ONS-12 glioma cells were suspended in saline and transcutaneously inoculated into the cisterna magna of BALB/c nu/nu mice using a 27-gauge needle. The median survival times (MST) of MG models which were treated by intrathecal administration of 10(3) U of rIFN-beta and intraperitoneal injection of 10(4) U of rIFN-beta were 11.0 and 8.0 days, compared with an MST of 7 days for control mice. The rIFN-beta was not effective by intraperitoneal administration but was effective by intrathecal administration in the MG models. The MSTs of MG models which were treated by administration of 10(5) U, 10(3) U of rIFN-beta and 0.1 ml saline were 15.0, 19.0 and 9.0 days, respectively. The therapeutic efficacy in MG models depended on the administration route of rIFN-beta, and as far as could be determined from the MG models, high-dose administration of rIFN-beta was not always useful.
Insights
Recombinant interferon-beta (rIFN-beta) showed antitumor effects on human glioma cells in vitro. Intrathecal administration of rIFN-beta improved survival in meningeal gliomatosis models, but efficacy varied with dose and route.
Area of Science:
- Oncology
- Immunology
- Neuroscience
Context:
- Glioblastomas are aggressive brain tumors with poor prognoses.
- Meningeal gliomatosis (MG) presents a significant therapeutic challenge.
- Recombinant interferon-beta (rIFN-beta) is an immunomodulatory cytokine with potential antitumor activity.
Purpose:
- To evaluate the in vitro and in vivo antitumor efficacy of rIFN-beta against human glioblastomas.
- To investigate the impact of administration route and dosage on rIFN-beta's therapeutic effect in MG models.
Summary:
- In vitro studies demonstrated that rIFN-beta suppressed human glioma cell lines (ONS-12 and ONS-20) at low doses.
- In vivo meningeal gliomatosis models showed that intrathecal administration of rIFN-beta significantly increased median survival times (MST).
- Intraperitoneal administration of rIFN-beta was ineffective in MG models, and high-dose intrathecal administration was not consistently superior.
Impact:
- Intrathecal rIFN-beta shows promise as a localized treatment for meningeal gliomatosis.
- Optimizing administration route and dosage is crucial for maximizing rIFN-beta's therapeutic potential.
- Findings contribute to understanding rIFN-beta's role in brain tumor therapy.