Phosphoglucose isomerase/autocrine motility factor promotes melanoma cell migration through ERK activation dependent on autocrine production of interleukin-8.

It is well known that phosphoglucose isomerase/autocrine motility factor (AMF) promotes cell migration in an autocrine manner in various tumor cells. However, it remains unclear whether certain cytokines modulate the effects of AMF on tumor cell migration. Because interleukin (IL)-8, a proinflammatory cytokine, is produced by melanoma cells and has been correlated with melanoma migration, the migratory ability of melanoma cells induced by AMF may also involve induction of IL-8 expression. In the present study, we assessed whether AMF promotes melanoma cell migration through autocrine production of IL-8. We found that AMF stimulation increased IL-8 production through up-regulation of IL-8 mRNA transcription, especially in biologically early stage melanoma cells. AMF-induced migration of these cells was inhibited by a specific neutralizing antibody against IL-8. The IL-8 production induced by AMF was mediated by the ERK1/2 pathways. These findings suggest that melanoma migration induced by AMF is mediated by autocrine production of IL-8 as a novel downstream modulator of the AMF signaling pathway.

Fascin expression is correlated with tumor progression of extrahepatic bile duct cancer.

BACKGROUND/AIMS: Fascin, an actin-crosslinking protein, participates in cell motility. Fascin over-expression induces a high potential for invasion and metastasis in various malignancies. The aim of this study was to determine the relationship of fascin expression to clinicopathological findings in patients with extrahepatic bile duct cancer. Furthermore, we investigated the correlation between fascin expression and intracellular adhesion molecular (E-cadherin and beta-catenin). METHODOLOGY: We evaluated the expression of fascin, E-cadherin and beta-catenin by immunohistochemistry in surgical specimens from 26 patients with extrahepatic bile duct cancer. RESULTS: Normal epithelial cells of the bile duct was not immunoreactive for fascin, and cancer cells often show immunoreactivity, which was found more frequently at the invasive tumor fronts than at other tumor areas. The present study demonstrated a statistically significant correlation between fascin expression and gender, tumor status, vascular invasion, and disease stage. We detected that increased immunoreactivity for fascin had tendencies to disrupt membranous immunoreactivity for E-cadherin and beta-catenin. CONCLUSIONS: We conclude that fascin expression is correlated with tumor progression. The expression of fascin is frequently detected at the invasive tumor fronts, indicating that invading tumor cells express fascin abundantly. In tumor cells with an over-expression of fascin, E-cadherin and betacatenin expressions often disrupt membranous immunoreactivity.

Implication of galectin-3 in Wnt signaling.

Galectin-3 (gal-3), a member of the beta-galactoside-binding proteins family, was identified as a binding partner of beta-catenin. Analysis of the human gal-3 sequence reveled a structural similarity to beta-catenin as it also contains the consensus sequence (S92XXXS96) for glycogen synthase kinase-3beta (GSK-3beta) phosphorylation and can serve as its substrate. In addition, Axin, a regulator protein of Wnt that complexes with beta-catenin, also binds gal-3 using the same sequence motif identified here by a deletion mutant analysis. The data presented here give credence to the suggestion that gal-3 is a key regulator in the Wnt/beta-catenin signaling pathway and highlight the functional similarities between gal-3 and beta-catenin.

Reduced galectin-3 expression is an indicator of unfavorable prognosis in gastric cancer.

BACKGROUND: Galectin-3 (gal-3) participates in a variety of biological events, including cell adhesion, proliferation, differentiation and apoptosis. The aim of this study was to determine the relationship of gal-3 expression with clinicopathological findings and prognosis in patients with gastric cancer. PATIENTS AND METHODS: Gal-3 and Ki-67 expressions were assessed by immunohistochemistry in 115 patients with gastric cancer. PCR-single strand conformation polymorphism (SSCP)-sequence analysis and the levels of gal-3 mRNA were also examined. RESULTS: The present study demonstrated that gal-3 expression was correlated with nodal status, lymphatic inivasion, pathological stage and histological parameters. On the other hand, gal-3 expression did not correlate with the expression of Ki-67. Reduced expression of gal-3 was significantly associated with a poor prognosis and multivariate analysis showed that gal-3 expression was an independent prognostic factor. On PCR-SSCP-sequence analysis, 2 single nucleotide polymorphisms (SNPs) were detected in the gal-3 gene, but none showed mutations. CONCLUSION: Reduced gal-3 expression was associated with lymph node metastasis, advanced stage and tumor differentiation in gastric cancer. Gal-3 expression could be a useful prognostic factor in gastric cancer.

Hyperbaric oxygenation promotes regeneration of biliary cells and improves cholestasis in rats.

AIM: To investigate the effects of hyperbaric oxygenation (HBO) on regeneration of the biliary ductal system and postoperative cholestasis in hepatectomized rats. METHODS: HBO was performed in Wistar rats daily starting 12 h after a 70% partial hepatectomy. Regenerated liver weight, serum parameters and the proliferating cell nuclear antigen labeling index of hepatocytes and biliary ductal cells were measured. Hepatocyte growth factor (HGF), c-Met and transforming growth factor (TGF) ß-1 mRNA expression levels were analyzed by quantitative reverse transcription polymerase chain reaction. RESULTS: HBO improved the postoperative serum levels of total bile acid but not transaminase levels. HBO promoted hepatocyte and biliary ductal cell proliferation. The hematoxylin and eosin-stained specimens revealed fewer ballooned hepatocytes and higher cell densities in the HBO group compared to the control group. HBO suppressed c-Met mRNA levels at 15 h but did not modulate HGF or TGF ß-1 mRNA expression levels. CONCLUSION: HBO promoted regeneration of biliary ductal cells and improved postoperative cholestasis after a partial hepatectomy.

Trans-ileocecal portal vein embolization as a preoperative treatment for right trisegmentectomy with caudate lobectomy.

BACKGROUND AND OBJECTIVES: The indication of preoperative portal vein embolization (PVE) has been expanded to hepatocellular carcinoma, cholangiocellular carcinoma (CCC), hepatic metastasis, and gallbladder (GB) cancer as well as hilar cholangiocarcinoma (hCC). However, biliary cancers sometimes cause peritoneal dissemination. PATIENTS AND METHODS: We performed our preoperative trans-ileocecal-vein PVE (TIPE) method on 14 (3 GB cancer, 1 CCC, and 10 hCC), whose estimated residual liver volume was <30%. RESULTS: Out of 14 patients, peritoneal dissemination was encountered in two patients with GB cancer and one with hCC (21.4%) during our procedure. The estimated residual liver volume was 37.4 +/- 2.7% at 14 days after PVE in patients without predisposing cholangitis, while those in patients with cholangitis was 29.3 +/- 1.3% (P = 0.0002). No major complication due to the procedure was encountered in this series. CONCLUSIONS: PTPE could be the first choice for patients with hCC, hepatocellular carcinoma, and hepatic metastases. Although the TIPE proposed here has some potential disadvantages, we would recommend it especially for patients with GB cancer because of its high potential to cause cancerous peritonitis. When a patient had predisposing cholangitis, radical operation should be scheduled on >21 days after PVE rather than on 14 days.