Cell-based therapy using adult mesenchymal stem cells (MSCs) has already been the subject of clinical trials, but for further development and optimization the distribution and integration of the engrafted cells into host tissues have to be monitored. Today, for this purpose magnetic resonance imaging (MRI) is the most suitable technique, and micron-sized iron oxide particles (MPIOs) used for labeling are favorable due to their low detection limit. However, constitutional data concerning labeling efficiency, cell viability, and function are lacking. We demonstrate that cell viability and migratory potential of bone marrow mesenchymal stromal cells (BMSCs) are negatively correlated with incorporated MPIOs, presumably due to interference with the actin cytoskeleton. Nevertheless, labeling of BMSCs with low amounts of MPIOs results in maintained cellular function and sufficient contrast for in vivo observation of single cells by MRI in a rat glioma model. Conclusively, though careful titration is indicated, MPIOs are a promising tool for in vivo cell tracking and evaluation of cell-based therapies.
To evaluate in a single center retrospectively the efficacy and tolerability of a weekly regimen, which alternates temozolomide (TMZ) in patients with recurrent or progressive high-grade glioma (HGG). From January 2005 until June 2011, 54 patients with recurrent or progressive HGG were treated with TMZ 150 mg/m²/day on days 1-7 and 15-21 of a 28-day cycle ("one week on-one week off" scheme; TMZ 7/14) with individual dose adjustment depending on toxicity. The majority of patients (n = 48, 89 %) was treated at first tumor recurrence or progression. All patients had received prior radiotherapy with or without concomitantly administered TMZ and, optionally, adjuvant chemotherapy. After initiation of TMZ 7/14, MRI was obtained every 8-12 weeks. Tumor response or progression was assessed according to Macdonald criteria. Blood examinations were performed weekly. Toxicity was evaluated according to Common Terminology Criteria for Adverse Events (CTCAE; version 3.0). A total of 434 treatment weeks with TMZ 7/14 were delivered. The median number of treatment weeks was 7 (range, 1-41 weeks). No grade 4 hematological toxicity and no opportunistic infections occurred. Patients with neutropenia were not observed. Two patients developed grade 3 and 4 patients grade 2 leukocytopenia. Thrombocytopenia grade 3 and grade 2 occurred in 4 patients and 6 patients, respectively. The progression-free survival (PFS) rate at 6 months was 43 %. Median PFS from treatment initiation was 18 weeks (95 % CI, 14-22 weeks) and median overall survival (OS) was 37 weeks (95 % CI, 31-42 weeks). The rates for PFS and OS at 1 year were 24 and 28 %, respectively. Our data suggest that treatment with TMZ 7/14 is safe and effective in patients with recurrent or progressive HGG.
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