Use of apparent diffusion coefficients in evaluating the response of vestibular schwannomas to Gamma Knife surgery.

OBJECT: Cellular density is a major factor responsible for changes in apparent diffusion coefficients (ADCs). The authors hypothesized that loss of tumor cells after Gamma Knife surgery (GKS) might alter ADC values. Magnetic resonance imaging, including diffusion-weighted (DW) imaging, was performed to detect cellular changes in brain tumors so that the authors could evaluate the tumor response to GKS as well as the efficacy of the procedure. METHODS: The authors conducted a prospective trial involving 31 patients harboring solid or cystic vestibular schwannomas (VSs) that were treated with GKS. The patients underwent serial MR imaging, including DW imaging, before GKS and at multiple intervals following the procedure. The authors observed the patients over time, evaluating MR imaging findings and clinical outcomes at 6-month intervals. The ADCs were calculated from echo-planar DW images, and mean ADC values were compared at each follow-up. RESULTS: The mean follow-up period was 36.5 months (range 18-60 months). Imaging studies showed a reduction in tumor volume in 19 patients (61.3%) and tumor growth arrest in 9 patients (29%). In the remaining 3 patients (9.7%), tumor enlargement was documented at 18, 36, and 42 months. The mean ADC value before GKS for all solid VSs was 1.06 ± 0.17 × 10(-3) mm(2)/second, which significantly increased 6 months after GKS and continued to increase with time (p = 0.0086). The mean ADC value for treated solid tumors as of the last mean follow-up of 36 months (range 18-60 months) was 1.72 ± 0.26 × 10(-3) mm(2)/second (range 1.50-2.09 × 10(-3) mm(2)/second), which was significantly higher than that before GKS (p = 0.0001). Tumor volumes were positively related to ADC values (p = 0.03). The mean ADC value before GKS for all cystic VSs was 2.09 ± 0.24 × 10(-3) mm(2)/second (range 1.80-2.58 × 10(-3) mm(2)/second). The mean ADC value for treated cystic tumors as of the last mean follow-up of 38 months (range 18-48 months) was 1.89 ± 0.22 × 10(-3) mm(2)/second. In 3 patients harboring solid VSs, the tumor enlarged after GKS but the ADC values were higher than those before GKS. The authors considered these tumors to be controlled and continued follow-up in the patients. CONCLUSIONS: Apparent diffusion coefficient values may be useful for evaluating treatment results before any definite volume change is detected on imaging studies and for distinguishing radiation-induced necrosis from tumor recurrence in cases in which other imaging results are not definitive, as in cases of increased tumor volume or no volume change. The authors suggest that ADC measurements be included during routine MR imaging examinations for the evaluation of GKS results.

N-acetyltransferase is involved in baicalein-induced N-acetylation of 2-aminofluorene and DNA-2-aminofluorene adduct formation in human leukemia HL-60 cells.

Many arylamine and hydrazine drugs are acetylated by cytosolic N-acetyltransferase (NAT). The human promyelocytic leukemia cell line (HL-60) has been shown to acetylate arylamine and contain NAT activity. The purpose of this study was to determine whether or not baicalein could affect N-acetylation of 2-aminofluorene (AF) in HL-60 cells. Acetylated and nonacetylated AF were determined by using high performance liquid chromatography. Baicalein displayed a dose-dependent inhibition of cytosolic and intact cells' NAT activity and reduced the number of viable cells. Time-course experiments showed that N-acetylation of AF, measured from intact HL-60 cells, was inhibited by baicalein for up to 48 h. Baicalein also decreased AF-DNA adduct formation in the examined cells. The effects of baicalein on NAT were examined by flow cytometry and NAT gene expression was examined by polymerase chain reaction. The results demonstrated that baicalein inhibited NAT1 mRNA gene expression and reduced the level of NAT in HL-60 cells. These results show that baicalein can affect the NAT activity of human leukemia cells in vitro.