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. 2009 Mar 10;100(5):789-94.
doi: 10.1038/sj.bjc.6604933. Epub 2009 Feb 17.

Taurine: a potential marker of apoptosis in gliomas

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Taurine: a potential marker of apoptosis in gliomas

K S Opstad et al. Br J Cancer. .

Abstract

New cancer therapies are being developed that trigger tumour apoptosis and an in vivo method of apoptotic detection and early treatment response would be of great value. Magnetic resonance spectroscopy (MRS) can determine the tumour biochemical profile in vivo, and we have investigated whether a specific spectroscopic signature exists for apoptosis in human astrocytomas. High-resolution magic angle spinning (HRMAS) (1)H MRS provided detailed (1)H spectra of brain tumour biopsies for direct correlation with histopathology. Metabolites, mobile lipids and macromolecules were quantified from presaturation HRMAS (1)H spectra acquired from 41 biopsies of grades II (n=8), III (n=3) and IV (n=30) astrocytomas. Subsequently, TUNEL and H&E staining provided quantification of apoptosis, cell density and necrosis. Taurine was found to significantly correlate with apoptotic cell density (TUNEL) in both non-necrotic (R=0.727, P=0.003) and necrotic (R=0.626, P=0.0005) biopsies. However, the ca 2.8 p.p.m. polyunsaturated fatty acid peak, observed in other studies as a marker of apoptosis, correlated only in non-necrotic biopsies (R=0.705, P<0.005). We suggest that the taurine (1)H MRS signal in astrocytomas may be a robust apoptotic biomarker that is independent of tumour necrotic status.

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Figures

Figure 1
Figure 1
TUNEL-stained nuclei (dark staining) in a post-HRMAS non-necrotic astrocytoma biopsy sample.
Figure 2
Figure 2
Plots and linear regression analyses (±95% confidence limits) of TUNEL-positive nuclei per mm2 against taurine concentration (mM) for non-necrotic (closed symbols and solid lines, R=0.727, P=0.003, n=14) and necrotic astrocytoma biopsies (open symbols and dashed lines, R=0.626, P=0.0005, n=27).
Figure 3
Figure 3
Plots and linear regression analyses (±95% confidence limits) of TUNEL-positive nuclei per mm2 against (A) ca. 2.8 p.p.m. Lip/MM proton concentration for non-necrotic (closed symbols and solid lines, R=0.705, P<0.005) and necrotic astrocytoma biopsies (open symbols and dotted line showing the insignificant negative correlation); and (B) ca. 1.3 p.p.m. (closed symbols and solid line, R=0.703, P<0.005) and ca. 0.9 p.p.m. Lip/MM proton concentrations (open symbols and dashed line, R=0.676, P=0.008) for the non-necrotic biopsies only.
Figure 4
Figure 4
HRMAS 1H MRS from a non-necrotic (top) and necrotic (middle) biopsy showing the taurine and ca. 2.8 p.p.m. Lip/MM contributions. The bottom spectrum is an in vitro taurine HRMAS 1H MR spectrum showing the full taurine spectral pattern. Note that the biopsy spectra are slightly shifted to the right for full view of the spectral peaks.
Figure 5
Figure 5
Plots of TUNEL-positive nuclei per mm2 against cell density per mm2 for non-necrotic (closed symbols, n=14), necrotic astrocytoma biopsies with a percentage necrosis <25% (large open symbols, n=19) and necrotic astrocytoma biopsies with a percentage necrosis >50% (small open symbols, n=6).

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