Profound prevention of experimental brain metastases of breast cancer by temozolomide in an MGMT-dependent manner.

ABSTRACT:

Purpose

Brain metastases of breast cancer cause neurocognitive damage and are incurable. We evaluated a role for temozolomide in the prevention of brain metastases of breast cancer in experimental brain metastasis models.

Experimental design

Temozolomide was administered in mice following earlier injection of brain-tropic HER2-positive JIMT-1-BR3 and triple-negative 231-BR-EGFP sublines, the latter with and without expression of O(6)-methylguanine-DNA methyltransferase (MGMT). In addition, the percentage of MGMT-positive tumor cells in 62 patient-matched sets of breast cancer primary tumors and resected brain metastases was determined immunohistochemically.

Results

Temozolomide, when dosed at 50, 25, 10, or 5 mg/kg, 5 days per week, beginning 3 days after inoculation,

SUBMITTER: Palmieri D 

PROVIDER: S-EPMC4100541 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature