Clinical significance of stromal apoptosis in colorectal cancer

BackgroundEpithelial and stromal cells play an important role in the development of colorectal cancer (CRC). We aimed to determine the prognostic significance of both epithelial and stromal cell apoptosis in CRC.MethodsTotal apoptosis was determined by caspase-3 activity measurements in protein homogenates of CRC specimens and adjacent normal mucosa of 211 CRC patients. Epithelial apoptosis was determined by an ELISA specific for a caspase-3-degraded cytokeratin 18 product, the M30 antigen. Stromal apoptosis was determined from the ratio between total and epithelial apoptosis.ResultsEpithelial and stromal apoptosis, as well as total apoptosis, were significantly higher in CRC compared with corresponding adjacent normal mucosa. Low total tumour apoptosis (< or = median caspase-3 activity) was associated with a significantly worse disease recurrence (hazard ratio (HR), 95% confidence interval (95% CI): 1.77 (1.05-3.01)), independent of clinocopathological parameters. Epithelial apoptosis was not associated with clinical outcome. In contrast, low stromal apoptosis (< or = median caspase-3/M30) was found to be an independent prognostic factor for overall survival, disease-free survival and disease recurrence, with HRs (95% CI) of 1.66 (1.17-2.35), 1.62 (1.15-2.29) and 1.69 (1.01-2.85), respectively.InterpretationStromal apoptosis, in contrast to epithelial apoptosis, is an important factor with respect to survival and disease-recurrence in CRC

fMRI scanner noise interaction with affective neural processes

The purpose of the present study was the investigation of interaction effects between functional MRI scanner noise and affective neural processes. Stimuli comprised of psychoacoustically balanced musical pieces, expressing three different emotions (fear, neutral, joy). Participants (N=34, 19 female) were split into two groups, one subjected to continuous scanning and another subjected to sparse temporal scanning that features decreased scanner noise. Tests for interaction effects between scanning group (sparse/quieter vs continuous/noisier) and emotion (fear, neutral, joy) were performed. Results revealed interactions between the affective expression of stimuli and scanning group localized in bilateral auditory cortex, insula and visual cortex (calcarine sulcus). Post-hoc comparisons revealed that during sparse scanning, but not during continuous scanning, BOLD signals were significantly stronger for joy than for fear, as well as stronger for fear than for neutral in bilateral auditory cortex. During continuous scanning, but not during sparse scanning, BOLD signals were significantly stronger for joy than for neutral in the left auditory cortex and for joy than for fear in the calcarine sulcus. To the authors' knowledge, this is the first study to show a statistical interaction effect between scanner noise and affective processes and extends evidence suggesting scanner noise to be an important factor in functional MRI research that can affect and distort affective brain processes

MMP-2 and MMP-9 in normal mucosa are independently associated with outcome of colorectal cancer patients

BACKGROUND: Upregulation of the matrix metalloproteinases MMP-2 and MMP-9 in various cancers has been associated with worse survival of the patients. METHODS: We assessed MMP-2 and MMP-9 levels in normal colorectal mucosa from colorectal cancer patients in relation to the course of the disease. RESULTS: A high protein expression of MMP-2 as well as MMP-9 in normal mucosa was found to be correlated with worse 5-year survival. The combination of both parameters was an even stronger prognostic factor. These protein levels were found not to be related to the corresponding single nucleotide polymorphisms of MMP-2 (−1306C>T) and MMP-9 (−1562C>T). Multivariate analyses indicated that the MMP-2 and MMP-9 levels in normal mucosa are prognostic for survival, independent of TNM classification. CONCLUSION: MMP-2 and MMP-9 levels in normal mucosa are indicative of the course of disease in colorectal cancer patients