This study was performed to examine the usefulness of medical endoscopic imaging utilizing narrow-band illumination. The contrast between the vascular pattern and the adjacent mucosa of the underside of the human tongue was measured using five narrow-band illuminations and three broadband illuminations. The results demonstrate that the pathological features of a vascular pattern are dependent on the center wavelength and the bandwidth of illumination. By utilizing narrow-band illumination of 415+/-30 nm, the contrast of the capillary pattern in the superficial layer was markedly improved. This is an important benefit that is difficult to obtain with ordinary broadband illumination. The appearances of capillary patterns on color images were evaluated for three sets of filters. The narrow, band imaging (NBI) filter set (415+/-30 nm, 445+/-30 nm, 500+/-30 nm) was selected to achieve the preferred appearance of the vascular patterns for clinical tests. The results of clinical tests in colonoscopy and esophagoscopy indicated that NBI will be useful as a supporting method for observation of the endoscopic findings of early cancer.

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Aberrant activation and upregulation of the Wnt pathway is a key feature of many cancers. Wnt antagonists have recently attracted wide attention. Wnt inhibitory factor-1 (WIF-1) is a secreted antagonist that can bind to Wnt proteins directly and inhibit Wnt signaling pathway. It has been reported that WIF-1 expression is down regulated in several solid tumors and that WIF-1 is silenced by promoter hypermethylation in lung and colorectal cancer. By using RT-PCR, bisulfite sequence analysis, and methylation-specific PCR, we analysed expression and methylation of WIF-1 in cancer cell lines and freshly resected cancer tissues of the esophagus, stomach, colorectum, and pancreas. Downregulation of WIF-1 mRNA expression was observed in 61 (91.0%) of 67 cancer cell lines, 16 (80.0%) of 20 esophageal, 23 (74.2%) of 31 gastric, 41 (82.0%) of 50 colorectal, and six (75.0%) of eight pancreatic cancer tissues. Downregulation of WIF-1 expression was also observed at protein level. No significant association between WIF-1 downregulation and clinicopathological characteristics was found, suggesting that downregulation of WIF-1 expression is an early event in carcinogenesis of these cancers. Indeed, downregulation of WIF-1 expression was observed in 32 (72.7%) of 44 colorectal adenoma tissues and 18 (78.2%) of 23 early mucosal or submucosal colorectal carcinoma tissues. CpG island hypermethylation in the WIF-1 promoter region correlated with downregulation of WIF-1 expression in cancer cell lines and tissues. Treatment with demethylating agent, 5-aza-2 0 -deoxycytidine (5-aza-dC), restored WIF-1 expression in cancer cell lines. A combined treatment of 5-aza-dC and a histone deacetylase inhibitor, trichostatinA, restored WIF-1 expression synergistically, indicating the role of cytosine methylation and histone deacetylation in the silencing of the WIF-1 gene. Transfection of the WIF-1 gene construct into TE-1 esophageal cancer cell lines or SW48 colon cancer cell lines lacking WIF-1 expression resulted in a significant inhibition on colony formation, cell proliferation, anchorageindependent growth in soft agar. TOPflash assay showed WIF-1 inhibits Wnt canonical signaling in these cell lines.These results suggest tumor suppressive function of WIF-1, due to its ability to inhibit Wnt signaling. Our results suggest that WIF-1 silencing due to promoter hypermethylation is an important mechanism underlying aberrant activation of the Wnt signaling pathway in carcinogenesis of the digestive organs. Modulation of the Wnt pathway, through reversal of WIF-1 silencing by demethylating agents, is a potential target for treatment and/or prevention of gastrointestinal cancers.

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