The chemotherapeutic response of a murine (VM) model of human glioma

Abstract

Summary Using a cell line derived from the VM spontaneous murine astrocytoma, a reliable in vitro-in vivo model of human malignant glioma has been developed. In this paper we examine the effects of cytotoxic drugs with known activity against other animal brain tumour models and human disease on the in vivo VM model. The drugs BCNU, CCNU and vincristine produced significant volume reduction in tumours growing at a subcutaneous location in syngeneic animals. Procarbazine was ineffective. Similarly, BCNU, CCNU and vincristine produced small but statistically significant increases in survival of VM mice bearing the intracerebral tumour, but procarbazine was again ineffective. The modest, but significant, response of the VM model to the nitrosoureas mimics the human situation more closely than previously described animal models.A cell line VMDk 497-P(1), derived from the VM spontaneous murine astrocytoma (Fraser, 1980), has been used to develop an in vitro-in vivo model of human glioma. The cell line can be grown as monolayer cultures and as multicellular tumour spheroids (Bradford et al., 1989a). It also produces tumours at subcutaneous and intracranial sites when inoculated into syngeneic VM mice. In a previous report (Bradford et al., 1989b) we described the development of the in vivo model and showed that cell line 497-P(1) provides the basis for a reliable and reproducible model of glioma, which fulfils many of the criteria required for experimental therapy.

Lomustine and nimustine exert efficient antitumor effects against glioblastoma models with acquired temozolomide resistance

“… 36 The drug concentrations used in the previous study indicated above were similar to these amounts. 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 Eight mice were used for each treatment group (n = 8). The mice were euthanized when they demonstrated neurological signs such as hunched posture and/or they lost more than 20% body weight compared to the body weight on the day tumor cells were implanted.…”

“…Each of the drug concentrations was determined based on the clinical dose for human brain tumor treatment (TMZ, 150 mg/m 2 ; CCNU, 120‐130 mg/m 2 ; ACNU, 74‐111 mg/m 2 ) and calculated by converting these doses for the body surface area of mice 36 . The drug concentrations used in the previous study indicated above were similar to these amounts 17‐26 . Eight mice were used for each treatment group (n = 8).…”

“… 4 , 5 , 6 , 7 , 8 , 9 , 11 , 14 , 15 Therefore, in the present study, we investigated the anti–tumor effects of CCNU and ACNU on TMZ‐R‐GBM by employing GBM model cells with acquired TMZ resistance (TMZ‐R‐cells) to clarify whether or not CCNU and ACNU could be utilized as an alternative to TMZ in the therapy of TMZ‐R‐GBM. Moreover, because CCNU and ACNU have been used for a long time, several basic studies have been carried out on both CCNU 17 , 18 , 19 , 20 , 21 and ACNU 22 , 23 , 24 , 25 , 26 ; however, no investigations have directly examined or compared the effects of both drugs simultaneously. Hence, we conducted experiments to directly compare CCNU and ACNU under the same conditions both in vitro and in vivo, to determine their efficacy for TMZ‐R‐GBM.…”