Intracerebral chemotherapy in the 9L rat brain tumor model

Abstract

We have used the 9L rat brain tumor model to search for effective chemotherapeutic approaches to the management of brain tumors. Several antineoplastic agents which have been proposed or are currently being used for human brain tumors, including 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU), bleomycin, aziridinylbenzoquinone (AZQ), cis-Platinum, and acivicin, were administered intravenously (iv), intraperitoneally (ip), or intracerebrally (ic) to rats burdened with the intracranial 9L gliosarcoma. The results confirm that BCNU is the most effective systemic agent among the chemotherapeutic agents tested as indicated by its ability to significantly increase the median survival time (MST) and life span of the tumor-burdened animals. Bleomycin is an effective agent against the intracranial 9L tumor when administered ic. While neither systemic single iv dose AZQ (0.5-2.5 mg/kg) nor multiple ip treatments (0.5-1.0 mg/kg x 5, q 6 h) were effective in prolonging the survival, single ic dose AZQ (5-50 micrograms/rat) treatment significantly increased the MST of the treated animals (P< 0.05). Systemic AZQ treatments using higher doses produced a hematological toxicity, resulting in a decrease in MST of the treated animals. Cis-Platinum, either administered ip or ic, produced only a marginal effect on survival, although acute neurologic toxicity limited the dose of cis-Platinum that could be administered ic. Acivicin, either administered ip or ic, produced no effect on the survival of treated animals. Our results suggest that local treatment with certain antineoplastic agents may be an efficient therapy in the management of brain tumors.

Current Review of in Vivo GBM Rodent Models: Emphasis on the CNS-1 Tumour Model

“…It has been extensively used to study chemotherapy and radiation effects (Henderson et al, 1981; Wen et al, 1990; Kimler et al, 1992; Kruse et al, 1993). Recently, it has also been used to study tumour stem cells (Ghods et al, 2007).…”

Contributions of cell kill and posttreatment tumor growth rates to the repopulation of intracerebral 9L tumors after chemotherapy: An MRI study

“…These studies frequently use rodent brain tumor models (7)(8)(9)(10), particularly the rat 9L tumor (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29). Animal survival, colony-forming efficiency (CFE) assays of cells disaggregated from solid tumors, and measurements of excised tumor weights have been used for two decades to quantitate the efficacy of various treatments on the orthotopic 9L brain tumor (11)(12)(13)(14)(15)(16)(17)(18)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29). Numerous in vitro and in vivo studies have shown that 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) is an effective treatment for the 9L brain tumor (11-15, 17, 18, 20-23, 25-29); in fact, a single bolus of BCNU achieved a 3-4 log cell kill in orthotopic tumors, resulting in a 97% increase in life span (13).…”

Rat Brain Tumor Models and the Statistical Evaluation of Survival Data in Experimental Neuro-Oncology

“…It has been used extensively to evaluate the responses of brain tumors to a variety of therapeutic modalities, including chemotherapy (75)(76)(77)(78)(79), radiotherapy (75,80), combinations of chemo-and radiotherapy (22,77), immunotherapy (81)(82)(83)(84), the combination of chemo-and immunotherapy (85), effects of blood-brain barrier disruption on uptake of chemotherapeutic agents (69,70,86), boron neutron-capture therapy (BNCT) (87,88), and, most recently, for gene therapy (89)(90)(91)(92)(93)(94)(95)(96)(97)(98)(99)(100)(101)(102)(103)(104). Impressive therapeutic results have been obtained in a number of these studies, including eradication of the tumor.…”