Untitled

Abstract

Human low-grade gliomas represent a population of brain tumors that remain a therapeutic challenge. Preclinical evaluation of agents, to test their preventive or therapeutic efficacy in these tumors, requires the use of animal models. Spontaneous gliomas develop in models of chemically induced carcinogenesis, such as in the transplacental N-ethyl-N-nitrosourea (ENU) rat model. However, without the ability to detect initial tumor formation, multiplicity or to measure growth rates, it is difficult to test compounds for their interventional or preventional capabilities. In this study Fisher-334 rats, treated transplacentally with ENU, underwent magnetic resonance imaging (MRI) examination in order to evaluate this approach for detection of tumor formation and growth. ENU-induced intracranial cerebral tumors were first observable in T2-weighted images beginning at 4 months of age and grew with a mean doubling time of 0.487 +/- 0.112 months. These tumors were found histologically to be predominately mixed gliomas. Two therapeutic interventions were evaluated using MRI, vitamin A (all-trans retinol palmitate, RP), as a chemopreventative agent and the anti-angiogenic drug SU-5416. RP was found to significantly delay the time to first tumor observation by one month (P = 0.05). No differences in rates of tumor formation or growth rates were observed between control and RP-treated groups. MRI studies of rats treated with SU-5416 resulted in reduction in tumor growth rates compared to matched controls. These results show that MRI can be used to provide novel information relating to the therapeutic efficacy of agents against the ENU-induced tumor model.

Blockade of SDF-1 after irradiation inhibits tumor recurrences of autochthonous brain tumors in rats

“…To test our strategy to block SDF-1 interaction with both its receptors CXCR4 and CXCR7, we used N -ethyl- N -nitrosourea (ENU)–induced brain tumors in the Sprague-Dawley rat, a model that has proved to be extremely resistant to anticancer therapy in prior studies by a variety of investigators 17,18 (L. Recht, unpublished). After in utero exposure to ENU on days 17–18 of gestation, the pups appeared healthy for over 100 days, at which time they began to demonstrate neurological distress and die progressively from brain tumors from day 120 after birth.…”

Aptamer-Based In Vivo Therapeutic Targeting of Glioblastoma

“…To test NOX-A12 in vivo, the authors used N-ethyl-N-nitrosourea (ENU)-induced brain tumors in the Sprague-Dawley rat, a model that has been proven to be extremely resistant to anticancer therapy [110]. The authors demonstrated that NOX-A12-mediated SDF-1 blockade was indeed effective in inhibiting or delaying GBM recurrences following irradiation in this model.…”

Angiogenic Signalling Pathways Altered in Gliomas: Selection Mechanisms for More Aggressive Neoplastic Subpopulations with Invasive Phenotype

“…In order to follow the angiogenesis process during the neoplasia genesis, we have used an endogenous glioma model. It was generated by transplacental administration of ethylnitrosourea (ENU) in rats [28, 66, 67]. …”