Human brain tumor xenografts in nude mice as a chemotherapy model

Eur J Cancer Clin Oncol. 1983 Jun;19(6):799-805. doi: 10.1016/0277-5379(83)90012-3.

Abstract

Two human brain tumors which were previously established in nude mice were used to determine antitumor efficacy of various therapeutic agents. These tumors were a medulloblastoma (TE-671) and a glioma (U-251) with mass doubling times of 3.5 and 5.5 days respectively as subcutaneous implants in nude mice. Intracranial (i.c.) tumor challenge was accomplished by inoculating tissue culture-grown cells of either tumor into the right cerebral hemisphere to a depth of 3 mm. Median survival time (MST) in untreated mice with 10(5) i.c. injected TE-671 cells was approximately 30 days and 53 days in the U-251 tumor. With 2 X 10(5) U-251 tumor cells the MST was 27-31 days. Groups of mice which had been inoculated with tumor were treated with various doses and schedules of antineoplastic compounds by the i.p. route. The TE-671 tumor responded to AZQ treatment with an increase in life span (ILS) of 37% compared to untreated controls and an ILS of 30% with CCNU treatment. BCNU and PCNU were ineffective. With the U-251 tumor BCNU produced an ILS of greater than 60%, with 75% cures, greater than 112% ILS with PCNU and 49% ILS with CCNU. Neither tumor responded to procarbazine, PALA, dianhydrogalactitol, D-O-norleucine or dibromodulcitol. The U-251 tumor was treated on various schedules and doses with BCNU and found to respond well on late as well as early treatment. A new drug (rapamycin) being investigated by the NCI was found to be very effective against the U-251 tumor. This model system should prove valuable in assessing the effects of various chemotherapeutic modalities against brain tumors.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Brain Neoplasms / drug therapy*
  • Carmustine / therapeutic use
  • Disease Models, Animal*
  • Glioma / drug therapy
  • Humans
  • Medulloblastoma / drug therapy
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Neoplasms, Experimental / drug therapy
  • Polyenes / therapeutic use
  • Sirolimus
  • Transplantation, Heterologous

Substances

  • Antineoplastic Agents
  • Polyenes
  • Carmustine
  • Sirolimus