Cell death and oxidative stress in gliomas.
In gliomas, apoptosis and necrosis are determined by a number of promoting and inhibiting factors including oxidative cell stress mediated by nitric oxide synthases (NOS) and reduced by superoxide dismutases. Therefore, in 46 gliomas (including astrocytomas, oligodendrogliomas, oligo-astrocytomas, and glioblastomas), the relationship of apoptosis and necrosis and the expression of apoptosis-promoting (p53, bax, Fas, Fas-L) and inhibiting (bcl-2) factors as well as of different isoforms of NOS (NOSb, NOSe, NOSi) and manganese superoxide dismutase (MnSOD) were studied. Apoptosis was measured in situ by the TUNEL method while expression profiles of apoptosis-related and oxidative stress-associated factors were determined by immunohistochemistry. As a defining criterion, necrosis was restricted to glioblastomas while apoptosis increased with tumour malignancy (P=0.017) in all types of gliomas. Glial tumour cells displayed upregulation of bax, Fas, Fas-L, p53, and bcl-2 but with no significant correlation with malignancy. There was also a strong expression of NOS isoforms with upregulation of NOSe in all and of NOSb and NOSi in nearly 50% of the tumour specimens but only NOSb expression correlated significantly with tumour malignancy (P=0.004). Likewise, MnSOD was strongly expressed in all gliomas but was not correlated with tumour grade. There was a wide variability of expression in each tumour type without significant correlation between apoptosis and expression of apoptosis-associated or oxidative stress-related factors indicating that the network of regulating factors may be too complex for clear associations.
Tews
D S
DS
Division of Neuropathology, Johannes Gutenberg-University Medical Center, Mainz, Germany.
D000368:Aged; D001254:Astrocytoma / Q000473:pathology; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology*; D002277:Carcinoma / Q000473:pathology; D016923:Cell Death / Q000502:physiology; D053938:DNA Fragmentation; D005260:Female; D005909:Glioblastoma / Q000473:pathology; D005910:Glioma / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D008875:Middle Aged; D009837:Oligodendroglioma / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology*; D016612:Paraffin Embedding; D016707:Tissue Fixation